Skip to main content
    • Aa
    • Aa
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 97
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Aoki, Scott T. Kershner, Aaron M. Bingman, Craig A. Wickens, Marvin and Kimble, Judith 2016. PGL germ granule assembly protein is a base-specific, single-stranded RNase. Proceedings of the National Academy of Sciences, Vol. 113, Issue. 5, p. 1279.

    Boniecki, Michal J. Lach, Grzegorz Dawson, Wayne K. Tomala, Konrad Lukasz, Pawel Soltysinski, Tomasz Rother, Kristian M. and Bujnicki, Janusz M. 2016. SimRNA: a coarse-grained method for RNA folding simulations and 3D structure prediction. Nucleic Acids Research, Vol. 44, Issue. 7, p. e63.

    Castañeda, Alma D. Robinson, Donald A. Stevenson, Keith J. and Crooks, Richard M. 2016. Electrocatalytic amplification of DNA-modified nanoparticle collisions via enzymatic digestion. Chem. Sci.,

    Cheng, Kaiying Xu, Hong Chen, Xuanyi Wang, Liangyan Tian, Bing Zhao, Ye and Hua, Yuejin 2016. Structural basis for DNA 5´-end resection by RecJ. eLife, Vol. 5,

    Harris, Michael E. 2016. Theme and Variation in tRNA 5′ End Processing Enzymes: Comparative Analysis of Protein versus Ribonucleoprotein RNase P. Journal of Molecular Biology, Vol. 428, Issue. 1, p. 5.

    Kazlauskas, Darius Krupovic, Mart and Venclovas, Česlovas 2016. The logic of DNA replication in double-stranded DNA viruses: insights from global analysis of viral genomes. Nucleic Acids Research, Vol. 44, Issue. 10, p. 4551.

    Kel′in, Alexander V. Zlatev, Ivan Harp, Joel Jayaraman, Muthusamy Bisbe, Anna O′Shea, Jonathan Taneja, Nate Manoharan, Rajar M. Khan, Saeed Charisse, Klaus Maier, Martin A. Egli, Martin Rajeev, Kallanthottathil G. and Manoharan, Muthiah 2016. Structural Basis of Duplex Thermodynamic Stability and Enhanced Nuclease Resistance of 5′-C-Methyl Pyrimidine-Modified Oligonucleotides. The Journal of Organic Chemistry, Vol. 81, Issue. 6, p. 2261.

    Kim, Junsoo Sambalkhundev, Gerelt-Od Kim, Sulhee Son, Jonghyeon Han, Ah-reum Ko, Sul-Min Hwang, Kwang Yeon and Lee, Woo Cheol 2016. Processing of A-form ssDNA by cryptic RNase H fold exonuclease PF2046. Archives of Biochemistry and Biophysics, Vol. 606, p. 143.

    Kuo, Yin-Ming Henry, Ryan A. and Andrews, Andrew J. 2016. Measuring specificity in multi-substrate/product systems as a tool to investigate selectivity in vivo. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1864, Issue. 1, p. 70.

    Ogrizek, Mitja Konc, Janez Bren, Urban Hodošček, Milan and Janežič, Dušanka 2016. Role of magnesium ions in the reaction mechanism at the interface between Tm1631 protein and its DNA ligand. Chemistry Central Journal, Vol. 10, Issue. 1,

    Pereira, Mozart S. Murta, Bárbara Oliveira, Thaís C. F. Manfredi, Alex M. Nome, Faruk Hengge, Alvan C. and Brandão, Tiago A. S. 2016. Mechanistic Aspects of Phosphate Diester Cleavage Assisted by Imidazole. A Template Reaction for Obtaining Aryl Phosphoimidazoles. The Journal of Organic Chemistry,

    Prieto, Jesús Redondo, Pilar Merino, Nekane Villate, Maider Montoya, Guillermo Blanco, Francisco J. and Molina, Rafael 2016. Structure of the I-SceI nuclease complexed with its dsDNA target and three catalytic metal ions. Acta Crystallographica Section F Structural Biology Communications, Vol. 72, Issue. 6, p. 473.

    Samanta, Anirban and Medintz, Igor L. 2016. Nanoparticles and DNA – a powerful and growing functional combination in bionanotechnology. Nanoscale, Vol. 8, Issue. 17, p. 9037.

    Strauss, Benjamin B. Yab, Tracy C. O’Connor, Helen M. Taylor, William R. Mahoney, Douglas W. Simonson, Julie A. Christensen, John Chari, Suresh T. and Ahlquist, David A. 2016. Fecal Recovery of Ingested Cellular DNA: Implications for Noninvasive Detection of Upper Gastrointestinal Neoplasms. Digestive Diseases and Sciences, Vol. 61, Issue. 1, p. 117.

    Tateishi-Karimata, Hisae Muraoka, Takahiro Kinbara, Kazushi and Sugimoto, Naoki 2016. G-Quadruplexes with Tetra(ethylene glycol)-Modified Deoxythymidines are Resistant to Nucleases and Inhibit HIV-1 Reverse Transcriptase. ChemBioChem, Vol. 17, Issue. 15, p. 1399.

    Watanabe-Nakayama, Takahiro Itami, Masahiro Kodera, Noriyuki Ando, Toshio and Konno, Hiroki 2016. High-speed atomic force microscopy reveals strongly polarized movement of clostridial collagenase along collagen fibrils. Scientific Reports, Vol. 6, p. 28975.

    Wisniewski, Jessica A. Traore, Daouda A. Bannam, Trudi L. Lyras, Dena Whisstock, James C. and Rood, Julian I. 2016. TcpM: a novel relaxase that mediates transfer of large conjugative plasmids fromClostridium perfringens. Molecular Microbiology, Vol. 99, Issue. 5, p. 884.

    Zhang, Shuming Gu, Hong Chen, Haoyuan Strong, Emily Ollie, Edward W. Kellerman, Daniel Liang, Danni Miyagi, Masaru Anderson, Vernon E. Piccirilli, Joseph A. York, Darrin M. and Harris, Michael E. 2016. Isotope effect analyses provide evidence for an altered transition state for RNA 2′-O-transphosphorylation catalyzed by Zn2+. Chem. Commun., Vol. 52, Issue. 24, p. 4462.

    Aslan, Erhan and Arslanyolu, Muhittin 2015. Identification of neutral and acidic deoxyribonuclease activities in Tetrahymena thermophila life stages. European Journal of Protistology, Vol. 51, Issue. 2, p. 173.

    Dalhus, Bjørn Alseth, Ingrun and Bjørås, Magnar 2015. Structural basis for incision at deaminated adenines in DNA and RNA by endonuclease V. Progress in Biophysics and Molecular Biology, Vol. 117, Issue. 2-3, p. 134.


Nucleases: diversity of structure, function and mechanism

  • Wei Yang (a1)
  • DOI:
  • Published online: 21 September 2010

Nucleases cleave the phosphodiester bonds of nucleic acids and may be endo or exo, DNase or RNase, topoisomerases, recombinases, ribozymes, or RNA splicing enzymes. In this review, I survey nuclease activities with known structures and catalytic machinery and classify them by reaction mechanism and metal-ion dependence and by their biological function ranging from DNA replication, recombination, repair, RNA maturation, processing, interference, to defense, nutrient regeneration or cell death. Several general principles emerge from this analysis. There is little correlation between catalytic mechanism and biological function. A single catalytic mechanism can be adapted in a variety of reactions and biological pathways. Conversely, a single biological process can often be accomplished by multiple tertiary and quaternary folds and by more than one catalytic mechanism. Two-metal-ion-dependent nucleases comprise the largest number of different tertiary folds and mediate the most diverse set of biological functions. Metal-ion-dependent cleavage is exclusively associated with exonucleases producing mononucleotides and endonucleases that cleave double- or single-stranded substrates in helical and base-stacked conformations. All metal-ion-independent RNases generate 2′,3′-cyclic phosphate products, and all metal-ion-independent DNases form phospho-protein intermediates. I also find several previously unnoted relationships between different nucleases and shared catalytic configurations.

Corresponding author
*Author for correspondence: W. Yang, Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Bldg. 5, Rm B1-03, Bethesda, MD 20892, USA. Email:
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

J. Abelson , C. R. Trotta & H. Li (1998). tRNA splicing. Journal of Biological Chemistry 273, 1268512688.

P. L. Adams , M. R. Stahley , A. B. Kosek , J. Wang & S. A. Strobel (2004). Crystal structure of a self-splicing group I intron with both exons. Nature 430, 4550.

Y. Aizawa , Q. Xiang , A. M. Lambowitz & A. M. Pyle (2003). The pathway for DNA recognition and RNA integration by a group II intron retrotransposon. Molecular Cell 11, 795805.

F. Allemand , N. Mathy , D. Brechemier-Baey & C. Condon (2005). The 5S rRNA maturase, ribonuclease M5, is a Toprim domain family member. Nucleic Acids Research 33, 43684376.

B. Altermark , A. O. Smalas , N. P. Willassen & R. Helland (2006). The structure of Vibrio cholerae extracellular endonuclease I reveals the presence of a buried chloride ion. Acta Crystallographica D: Biological Crystallography 62, 13871391.

K. R. Andersen , A. T. Jonstrup , L. B. Van & D. E. Brodersen (2009). The activity and selectivity of fission yeast Pop2p are affected by a high affinity for Zn2+ and Mn2+ in the active site. RNA 15, 850861.

J. M. Andrade , V. Pobre , I. J. Silva , S. Domingues & C. M. Arraiano (2009). The role of 3′–5′ exoribonucleases in RNA degradation. Progress in Molecular Biology and Translation Sciences 85, 187229.

C. B. Anfinsen (1973). Principles that govern the folding of protein chains. Science 181, 223230.

L. Aravind & E. V. Koonin (1998). A novel family of predicted phosphoesterases includes Drosophila prune protein and bacterial RecJ exonuclease. Trends in Biochemical Sciences 23, 1719.

L. Aravind , D. D. Leipe & E. V. Koonin (1998). Toprim – a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. Nucleic Acids Research 26, 42054213.

V. L. Arcus , K. Backbro , A. Roos , E. L. Daniel & E. N. Baker (2004). Distant structural homology leads to the functional characterization of an archaeal PIN domain as an exonuclease. Journal of Biological Chemistry 279, 1647116478.

M. Ariyoshi , D. G. Vassylyev , H. Iwasaki , H. Nakamura , H. Shinagawa & K. Morikawa (1994). Atomic structure of the RuvC resolvase: a Holliday junction-specific endonuclease from E. coli. Cell 78, 10631072.

R. K. Arni , L. Watanabe , R. J. Ward , R. J. Kreitman , K. Kumar & F. G. Walz Jr. (1999). Three-dimensional structure of ribonuclease T1 complexed with an isosteric phosphonate substrate analogue of GpU: alternate substrate binding modes and catalysis. Biochemistry 38, 24522461.

P. J. Artymiuk , T. A. Ceska , D. Suck & J. R. Sayers (1997). Prokaryotic 5′–3′ exonucleases share a common core structure with gamma-delta resolvase. Nucleic Acids Research 25, 42244229.

H. P. Avey , M. O. Boles , C. H. Carlisle , S. A. Evans , S. J. Morris , R. A. Palmer , B. A. Woolhouse & S. Shall (1967). Structure of ribonuclease. Nature 213, 557562.

E. P. Baldwin , S. S. Martin , J. Abel , K. A. Gelato , H. Kim , P. G. Schultz & S. W. Santoro (2003). A specificity switch in selected cre recombinase variants is mediated by macromolecular plasticity and water. Chemistry and Biology 10, 10851094.

G. S. Baldwin , S. G. Waley & E. P. Abraham (1979). Identification of histidine residues that act as zinc ligands in beta-lactamase II by differential tritium exchange. Biochemical Journal 179, 459463.

C. Ban & W. Yang (1998a). Crystal structure and ATPase activity of MutL: implications for DNA repair and mutagenesis. Cell 95, 541552.

C. Ban & W. Yang (1998b). Structural basis for MutH activation in E. coli mismatch repair and relationship of MutH to restriction endonucleases. EMBO Journal 17, 15261534.

O. Barabas , D. R. Ronning , C. Guynet , A. B. Hickman , B. Ton-Hoang , M. Chandler & F. Dyda (2008). Mechanism of IS200/IS605 family DNA transposases: activation and transposon-directed target site selection. Cell 132, 208220.

D. H. Bechhofer (2009). Messenger RNA decay and maturation in Bacillus subtilis. Progress in Molecular Biology and Translation Sciences 85, 231273.

N. Beloglazova , G. Brown , M. D. Zimmerman , M. Proudfoot , K. S. Makarova , M. Kudritska , S. Kochinyan , S. Wang , M. Chruszcz , W. Minor , E. V. Koonin , A. M. Edwards , A. Savchenko & A. F. Yakunin (2008). A novel family of sequence-specific endoribonucleases associated with the clustered regularly interspaced short palindromic repeats. Journal of Biological Chemistry 283, 2036120371.

M. J. Benedik & U. Strych (1998). Serratia marcescens and its extracellular nuclease. FEMS Microbiology Letters 165, 113.

R. J. Bennett , H. J. Dunderdale & S. C. West (1993). Resolution of Holliday junctions by RuvC resolvase: cleavage specificity and DNA distortion. Cell 74, 10211031.

M. Bhagwat , L. J. Hobbs & N. G. Nossal (1997). The 5′-exonuclease activity of bacteriophage T4 RNase H is stimulated by the T4 gene 32 single-stranded DNA-binding protein, but its flap endonuclease is inhibited. Journal of Biological Chemistry 272, 2852328530.

A. G. Bhat , M. N. Leelaram , S. M. Hegde & V. Nagaraja (2009). Deciphering the distinct role for the metal coordination motif in the catalytic activity of Mycobacterium smegmatis topoisomerase I. Journal of Molecular Biology 393, 788802.

C. Biertümpfel , W. Yang & D. Suck (2007). Crystal structure of T4 endonuclease VII resolving a Holliday junction. Nature 449, 616620.

T. Biswas , H. Aihara , M. Radman-Livaja , D. Filman , A. Landy & T. Ellenberger (2005). A structural basis for allosteric control of DNA recombination by lambda integrase. Nature 435, 10591066.

J. Bitinaite , D. A. Wah , A. K. Aggarwal & I. Schildkraut (1998). FokI dimerization is required for DNA cleavage. Proceedings of the National Academy of Sciences USA 95, 1057010575.

M. G. Blanco , J. Matos , U. Rass , S. C. Ip & S. C. West (2010). Functional overlap between the structure-specific nucleases Yen1 and Mus81-Mms4 for DNA-damage repair in S. cerevisiae. DNA Repair (Amsterdam) 9, 394402.

P. Bork & C. Sander (1993). A hybrid protein kinase-RNase in an interferon-induced pathway? FEBS Letters 334, 149152.

C. A. Brautigam & T. A. Steitz (1998). Structural principles for the inhibition of the 3′–5′ exonuclease activity of Escherichia coli DNA polymerase I by phosphorothioates. Journal of Molecular Biology 277, 363377.

C. A. Brautigam , S. Sun , J. A. Piccirilli & T. A. Steitz (1999). Structures of normal single-stranded DNA and deoxyribo-3′-S-phosphorothiolates bound to the 3′–5′ exonucleolytic active site of DNA polymerase I from Escherichia coli. Biochemistry 38, 696704.

S. J. Brouns , M. M. Jore , M. Lundgren , E. R. Westra , R. J. Slijkhuis , A. P. Snijders , M. J. Dickman , K. S. Makarova , E. V. Koonin & J. Van Der Oost (2008). Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321, 960964.

M. Brucet , J. Querol-Audi , M. Serra , X. Ramirez-Espain , K. Bertlik , L. Ruiz , J. Lloberas , M. J. Macias , I. Fita & A. Celada (2007). Structure of the dimeric exonuclease TREX1 in complex with DNA displays a proline-rich binding site for WW domains. Journal of Biological Chemistry 282, 1454714557.

A. M. Buckle & A. R. Fersht (1994). Subsite binding in an RNase: structure of a barnase-tetranucleotide complex at 1·76-A resolution. Biochemistry 33, 16441653.

M. E. Budd , W. Choe & J. L. Campbell (2000). The nuclease activity of the yeast DNA2 protein, which is related to the RecB-like nucleases, is essential in vivo. Journal of Biological Chemistry 275, 1651816529.

K. A. Bunting , S. M. Roe , A. Headley , T. Brown , R. Savva & L. H. Pearl (2003). Crystal structure of the Escherichia coli dcm very-short-patch DNA repair endonuclease bound to its reaction product-site in a DNA superhelix. Nucleic Acids Research 31, 16331639.

K. Buttner , K. Wenig & K. P. Hopfner (2005). Structural framework for the mechanism of archaeal exosomes in RNA processing. Molecular Cell 20, 461471.

S. Buttner , T. Eisenberg , D. Carmona-Gutierrez , D. Ruli , H. Knauer , C. Ruckenstuhl , C. Sigrist , S. Wissing , M. Kollroser , K. U. Frohlich , S. Sigrist & F. Madeo (2007). Endonuclease G regulates budding yeast life and death. Molecular Cell 25, 233246.

A. J. Callaghan , J. G. Grossmann , Y. U. Redko , L. L. Ilag , M. C. Moncrieffe , M. F. Symmons , C. V. Robinson , K. J. Mcdowall & B. F. Luisi (2003). Quaternary structure and catalytic activity of the Escherichia coli ribonuclease E amino-terminal catalytic domain. Biochemistry 42, 1384813855.

A. J. Callaghan , M. J. Marcaida , J. A. Stead , K. J. Mcdowall , W. G. Scott & B. F. Luisi (2005). Structure of Escherichia coli RNase E catalytic domain and implications for RNA turnover. Nature 437, 11871191.

I. Callebaut , D. Moshous , J. P. Mornon & J. P. De Villartay (2002). Metallo-beta-lactamase fold within nucleic acids processing enzymes: the beta-CASP family. Nucleic Acids Research 30, 35923601.

K. Calvin & H. Li (2008). RNA-splicing endonuclease structure and function. Cell Mol Life Sci 65, 11761185.

K. Calvin , S. Xue , C. Ellis , M. H. Mitchell & H. Li (2008). Probing the catalytic triad of an archaeal RNA splicing endonuclease. Biochemistry 47, 1365913665.

S. Carr , D. Walker , R. James , C. Kleanthous & A. M. Hemmings (2000). Inhibition of a ribosome-inactivating ribonuclease: the crystal structure of the cytotoxic domain of colicin E3 in complex with its immunity protein. Structure 8, 949960.

J. Carte , R. Wang , H. Li , R. M. Terns & M. P. Terns (2008). Cas6 is an endoribonuclease that generates guide RNAs for invader defense in prokaryotes. Genes and Development 22, 34893496.

V. M. Castillo-Acosta , L. M. Ruiz-Perez , W. Yang , D. Gonzalez-Pacanowska & A. E. Vidal (2009). Identification of a residue critical for the excision of 3′-blocking ends in apurinic/apyrimidinic endonucleases of the Xth family. Nucleic Acids Research 37, 18291842.

S. M. Cerritelli & R. J. Crouch (2009). Ribonuclease H: the enzymes in eukaryotes. FEBS Journal 276, 14941505.

S. Ceschini , A. Keeley , M. S. Mcalister , M. Oram , J. Phelan , L. H. Pearl , I. R. Tsaneva & T. E. Barrett (2001). Crystal structure of the fission yeast mitochondrial Holliday junction resolvase Ydc2. EMBO Journal 20, 66016611.

T. A. Ceska , J. R. Sayers , G. Stier & D. Suck (1996). A helical arch allowing single-stranded DNA to thread through T5 5′-exonuclease. Nature 382, 9093.

J. J. Champoux (2001). DNA topoisomerases: structure, function, and mechanism. Annual Review of Biochemistry 70, 369413.

J. J. Champoux & S. J. Schultz (2009). Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription. FEBS Journal 276, 15061516.

G. Chanfreau , S. M. Noble & C. Guthrie (1996). Essential yeast protein with unexpected similarity to subunits of mammalian cleavage and polyadenylation specificity factor (CPSF). Science 274, 15111514.

J. H. Chang , J. J. Kim , J. M. Choi , J. H. Lee & Y. Cho (2008). Crystal structure of the Mus81–Eme1 complex. Genes and Development 22, 10931106.

A. Changela , R. J. Digate & A. Mondragon (2001). Crystal structure of a complex of a type IA DNA topoisomerase with a single-stranded DNA molecule. Nature 411, 10771081.

B. R. Chapados , D. J. Hosfield , S. Han , J. Qiu , B. Yelent , B. Shen & J. A. Tainer (2004). Structural basis for FEN-1 substrate specificity and PCNA-mediated activation in DNA replication and repair. Cell 116, 3950.

D. K. Chatterjee , A. W. Hammond , R. W. Blakesley , S. M. Adams & G. F. Gerard (1991). Genetic organization of the KpnI restriction–modification system. Nucleic Acids Research 19, 65056509.

D. S. Chen , T. Herman & B. Demple (1991). Two distinct human DNA diesterases that hydrolyze 3′-blocking deoxyribose fragments from oxidized DNA. Nucleic Acids Research 19, 59075914.

W. J. Chen , P. J. Lai , Y. S. Lai , P. T. Huang , C. C. Lin & T. H. Liao (2007a). Probing the catalytic mechanism of bovine pancreatic deoxyribonuclease I by chemical rescue. Biochemical and Biophysical Research Communications 352, 689696.

W. J. Chen & T. H. Liao (2006). Structure and function of bovine pancreatic deoxyribonuclease I. Protein and Peptide Letters 13, 447453.

X. Chen , N. Li & A. D. Ellington (2007b). Ribozyme catalysis of metabolism in the RNA world. Chemistry and Biodiversity 4, 633655.

Y. Chen , U. Narendra , L. E. Iype , M. M. Cox & P. A. Rice (2000). Crystal structure of a Flp recombinase-Holliday junction complex: assembly of an active oligomer by helix swapping. Molecular Cell 6, 885897.

Y. C. Chen , G. L. Shipley , T. K. Ball & M. J. Benedik (1992). Regulatory mutants and transcriptional control of the Serratia marcescens extracellular nuclease gene. Molecular Microbiology 6, 643651.

C. Cheng , P. Kussie , N. Pavletich & S. Shuman (1998). Conservation of structure and mechanism between eukaryotic topoisomerase I and site-specific recombinases. Cell 92, 841850.

Y. Cheng & D. J. Patel (2004). Crystallographic structure of the nuclease domain of 3′hExo, a DEDDh family member, bound to rAMP. Journal of Molecular Biology 343, 305312.

Y. I. Chi , M. Martick , M. Lares , R. Kim , W. G. Scott & S. H. Kim (2008). Capturing hammerhead ribozyme structures in action by modulating general base catalysis. PLoS Biology 6, e234.

D. Chowdhury , P. J. Beresford , P. Zhu , D. Zhang , J. S. Sung , B. Demple , F. W. Perrino & J. Lieberman (2006). The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death. Molecular Cell 23, 133142.

D. W. Christianson (1991). Structural biology of zinc. Advances in Protein Chemistry 42, 281355.

C. Y. Chu & T. M. Rana (2007). Small RNAs: regulators and guardians of the genome. Journal of Cellular Physiology 213, 412419.

A. Ciccia , N. Mcdonald & S. C. West (2008). Structural and functional relationships of the XPF/MUS81 family of proteins. Annual Review of Biochemistry 77, 259287.

P. M. Clissold & C. P. Ponting (2000). PIN domains in nonsense-mediated mRNA decay and RNAi. Current Biology 10, R888890.

J. C. Cochrane & S. A. Strobel (2008). Catalytic strategies of self-cleaving ribozymes. Accounts of Chemical Research 41, 10271035.

C. Condon , D. Brechemier-Baey , B. Beltchev , M. Grunberg-Manago & H. Putzer (2001). Identification of the gene encoding the 5S ribosomal RNA maturase in Bacillus subtilis: mature 5S rRNA is dispensable for ribosome function. RNA 7, 242253.

C. C. Correll , X. Yang , T. Gerczei , J. Beneken & M. J. Plantinga (2004). RNA recognition and base flipping by the toxin sarcin. Journal of Synchrotron Radiation 11, 9396.

J. A. Cowan (2002). Structural and catalytic chemistry of magnesium-dependent enzymes. Biometals 15, 225235.

Y. J. Crow , B. E. Hayward , R. Parmar , P. Robins , A. Leitch , M. Ali , D. N. Black , H. Van Bokhoven , H. G. Brunner , B. C. Hamel , P. C. Corry , F. M. Cowan , S. G. Frints , J. Klepper , J. H. Livingston , S. A. Lynch , R. F. Massey , J. F. Meritet , J. L. Michaud , G. Ponsot , T. Voit , P. Lebon , D. T. Bonthron , A. P. Jackson , D. E. Barnes & T. Lindahl (2006a). Mutations in the gene encoding the 3′–5′ DNA exonuclease TREX1 cause Aicardi–Goutieres syndrome at the AGS1 locus. Nature Genetics 38, 917920.

Y. J. Crow , A. Leitch , B. E. Hayward , A. Garner , R. Parmar , E. Griffith , M. Ali , C. Semple , J. Aicardi , R. Babul-Hirji , C. Baumann , P. Baxter , E. Bertini , K. E. Chandler , D. Chitayat , D. Cau , C. Dery , E. Fazzi , C. Goizet , M. D. King , J. Klepper , D. Lacombe , G. Lanzi , H. Lyall , M. L. Martinez-Frias , M. Mathieu , C. Mckeown , A. Monier , Y. Oade , O. W. Quarrell , C. D. Rittey , R. C. Rogers , A. Sanchis , J. B. Stephenson , U. Tacke , M. Till , J. L. Tolmie , P. Tomlin , T. Voit , B. Weschke , C. G. Woods , P. Lebon , D. T. Bonthron , C. P. Ponting & A. P. Jackson (2006b). Mutations in genes encoding ribonuclease H2 subunits cause Aicardi–Goutieres syndrome and mimic congenital viral brain infection. Nature Genetics 38, 910916.

Y. J. Crow & J. Rehwinkel (2009). Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity. Human Molecular Genetics 18, R130R136.

I. A. Cymerman , A. Obarska , K. J. Skowronek , A. Lubys & J. M. Bujnicki (2006). Identification of a new subfamily of HNH nucleases and experimental characterization of a representative member, HphI restriction endonuclease. Proteins 65, 867876.

H. Daiyasu , K. Osaka , Y. Ishino & H. Toh (2001). Expansion of the zinc metallo-hydrolase family of the beta-lactamase fold. FEBS Letters 503, 16.

S. Datta , C. Larkin & J. F. Schildbach (2003). Structural insights into single-stranded DNA binding and cleavage by F factor TraI. Structure 11, 13691379.

D. R. Davies , I. Y. Goryshin , W. S. Reznikoff & I. Rayment (2000). Three-dimensional structure of the Tn5 synaptic complex transposition intermediate. Science 289, 7785.

D. R. Davies , H. Interthal , J. J. Champoux & W. G. Hol (2004). Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexes. Journal of Medicinal Chemistry 47, 829837.

D. R. Davies , A. Mushtaq , H. Interthal , J. J. Champoux & W. G. Hol (2006). The structure of the transition state of the heterodimeric topoisomerase I of Leishmania donovani as a vanadate complex with nicked DNA. Journal of Molecular Biology 357, 12021210.

I. L. De La Sierra-Gallay , O. Pellegrini & C. Condon (2005). Structural basis for substrate binding, cleavage and allostery in the tRNA maturase RNase Z. Nature 433, 657661.

U. De Silva , S. Choudhury , S. L. Bailey , S. Harvey , F. W. Perrino & T. Hollis (2007). The crystal structure of TREX1 explains the 3′ nucleotide specificity and reveals a polyproline II helix for protein partnering. Journal of Biological Chemistry 282, 1053710543.

A. C. Declais & D. M. Lilley (2008). New insight into the recognition of branched DNA structure by junction-resolving enzymes. Current Opinion in Structural Biology 18, 8695.

B. Demple & L. Harrison (1994). Repair of oxidative damage to DNA: enzymology and biology. Annual Review of Biochemistry 63, 915948.

N. A. Desai & V. Shankar (2003). Single-strand-specific nucleases. FEMS Microbiology Reviews 26, 457491.

R. A. Deshpande & V. Shankar (2002). Ribonucleases from T2 family. Critical Reviews in Microbiology 28, 79122.

M. P. Deutscher & Z. Li (2001). Exoribonucleases and their multiple roles in RNA metabolism. Progress in Nucleic Acid Research and Molecular Biology 66, 67105.

M. P. Deutscher , G. T. Marshall & H. Cudny (1988). RNase PH: an Escherichia coli phosphate-dependent nuclease distinct from polynucleotide phosphorylase. Proceedings of the National Academy of Sciences USA 85, 47104714.

J. M. Devos , S. J. Tomanicek , C. E. Jones , N. G. Nossal & T. C. Mueser (2007). Crystal structure of bacteriophage T4 5′ nuclease in complex with a branched DNA reveals how flap endonuclease-1 family nucleases bind their substrates. Journal of Biological Chemistry 282, 3171331724.

R. L. Diaz , A. D. Alcid , J. M. Berger & S. Keeney (2002). Identification of residues in yeast Spo11p critical for meiotic DNA double-strand break formation. Molecular and Cellular Biology 22, 11061115.

H. Diebler , M. Eigen , G. Ilgenfritz , G. Maass & R. Winkler (1969). Kinetics and mechanisms of reactions of main group metal ions with biological carriers. Pure Applied Chemistry 20, 93115.

M. S. Dillingham & S. C. Kowalczykowski (2008). RecBCD enzyme and the repair of double-stranded DNA breaks. Microbiology and Molecular Biology Reviews 72, 642671, Table of Contents.

P. L. Domanico & Y. C. Tse-Dinh (1991). Mechanistic studies on E. coli DNA topoisomerase I: divalent ion effects. Journal of Inorganic Biochemistry 42, 8796.

Z. Dominski (2007). Nucleases of the metallo-beta-lactamase family and their role in DNA and RNA metabolism. Critical Reviews in Biochemistry and Molecular Biology 42, 6793.

B. Dong , M. Niwa , P. Walter & R. H. Silverman (2001). Basis for regulated RNA cleavage by functional analysis of RNase L and Ire1p. RNA 7, 361373.

K. C. Dong & J. M. Berger (2007). Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature 450, 12011205.

J. A. Doudna & T. R. Cech (2002). The chemical repertoire of natural ribozymes. Nature 418, 222228.

D. T. Dryden , N. E. Murray & D. N. Rao (2001). Nucleoside triphosphate-dependent restriction enzymes. Nucleic Acids Research 29, 37283741.

X. Duan , F. S. Gimble & F. A. Quiocho (1997). Crystal structure of PI-SceI, a homing endonuclease with protein splicing activity. Cell 89, 555564.

V. Duppatla , C. Bodda , C. Urbanke , P. Friedhoff & D. N. Rao (2009). The C-terminal domain is sufficient for endonuclease activity of Neisseria gonorrhoeae MutL. Biochemical Journal 423, 265277.

F. Dyda , A. B. Hickman , T. M. Jenkins , A. Engelman , R. Craigie & D. R. Davies (1994). Crystal structure of the catalytic domain of HIV-1 integrase: similarity to other polynucleotidyl transferases. Science 266, 19811986.

A. Dziembowski , E. Lorentzen , E. Conti & B. Seraphin (2007). A single subunit, Dis3, is essentially responsible for yeast exosome core activity. Nature Structural and Molecular Biology 14, 1522.

A. B. Eberle , S. Lykke-Andersen , O. Muhlemann & T. H. Jensen (2009). SMG6 promotes endonucleolytic cleavage of nonsense mRNA in human cells. Nature Structural and Molecular Biology 16, 4955.

A. Ebihara , M. Yao , R. Masui , I. Tanaka , S. Yokoyama & S. Kuramitsu (2006). Crystal structure of hypothetical protein TTHB192 from Thermus thermophilus HB8 reveals a new protein family with an RNA recognition motif-like domain. Protein Science 15, 14941499.

F. Eckstein (1985). Nucleoside phosphorothioates. Annual Review of Biochemistry 54, 367402.

E. Falvey , G. F. Hatfull & N. D. Grindley (1988). Uncoupling of the recombination and topoisomerase activities of the gamma delta resolvase by a mutation at the crossover point. Nature 332, 861863.

T. A. Farazi , S. A. Juranek & T. Tuschl (2008). The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members. Development 135, 12011214.

S. Fekairi , S. Scaglione , C. Chahwan , E. R. Taylor , A. Tissier , S. Coulon , M. Q. Dong , C. Ruse , J. R. Yates 3RD, P. Russell , R. P. Fuchs , C. H. Mcgowan & P. H. Gaillard (2009). Human SLX4 is a Holliday junction resolvase subunit that binds multiple DNA repair/recombination endonucleases. Cell 138, 7889.

R. A. Fekete & L. S. Frost (2000). Mobilization of chimeric oriT plasmids by F and R100-1: role of relaxosome formation in defining plasmid specificity. Journal of Bacteriology 182, 40224027.

A. R. Fersht & V. Daggett (2002). Protein folding and unfolding at atomic resolution. Cell 108, 573582.

T. J. Fiedler , H. A. Vincent , Y. Zuo , O. Gavrialov & A. Malhotra (2004). Purification and crystallization of Escherichia coli oligoribonuclease. Acta Crystallographica D: Biological Crystallography 60, 736739.

K. M. Flaherty , D. B. Mckay , W. Kabsch & K. C. Holmes (1991). Similarity of the three-dimensional structures of actin and the ATPase fragment of a 70-kDa heat shock cognate protein. Proceedings of the National Academy of Sciences USA 88, 50415045.

J. M. Fogg , M. Kvaratskhelia , M. F. White & D. M. Lilley (2001). Distortion of DNA junctions imposed by the binding of resolving enzymes: a fluorescence study. Journal of Molecular Biology 313, 751764.

C. Frazao , C. E. Mcvey , M. Amblar , A. Barbas , C. Vonrhein , C. M. Arraiano & M. A. Carrondo (2006). Unravelling the dynamics of RNA degradation by ribonuclease II and its RNA-bound complex. Nature 443, 110114.

P. S. Freemont , J. M. Friedman , L. S. Beese , M. R. Sanderson & T. A. Steitz (1988). Cocrystal structure of an editing complex of Klenow fragment with DNA. Proceedings of the National Academy of Sciences USA 85, 89248928.

P. Friedhoff , B. Kolmes , O. Gimadutdinow , W. Wende , K. L. Krause & A. Pingoud (1996). Analysis of the mechanism of the Serratia nuclease using site-directed mutagenesis. Nucleic Acids Research 24, 26322639.

K. Fukui , M. Nishida , N. Nakagawa , R. Masui & S. Kuramitsu (2008). Bound nucleotide controls the endonuclease activity of mismatch repair enzyme MutL. Journal of Biological Chemistry 283, 1213612145.

H. W. Gabel & G. Ruvkun (2008). The exonuclease ERI-1 has a conserved dual role in 5·8S rRNA processing and RNAi. Nature Structural and Molecular Biology 15, 531533.

J. Gan , G. Shaw , J. E. Tropea , D. S. Waugh , D. L. Court & X. Ji (2008). A stepwise model for double-stranded RNA processing by ribonuclease III. Molecular Microbiology 67, 143154.

J. Gan , J. E. Tropea , B. P. Austin , D. L. Court , D. S. Waugh & X. Ji (2006). Structural insight into the mechanism of double-stranded RNA processing by ribonuclease III. Cell 124, 355366.

E. D. Garcin , D. J. Hosfield , S. A. Desai , B. J. Haas , M. Bjoras , R. P. Cunningham & J. A. Tainer (2008). DNA apurinic–apyrimidinic site binding and excision by endonuclease IV. Nature Structural and Molecular Biology 15, 515522.

J. Genschel , L. R. Bazemore & P. Modrich (2002). Human exonuclease I is required for 5′ and 3′ mismatch repair. Journal of Biological Chemistry 277, 1330213311.

K. Ghosh , F. Guo & G. D. Van Duyne (2007a). Synapsis of loxP sites by Cre recombinase. Journal of Biological Chemistry 282, 2400424016.

M. Ghosh , G. Meiss , A. M. Pingoud , R. E. London & L. C. Pedersen (2007b). The nuclease a-inhibitor complex is characterized by a novel metal ion bridge. Journal of Biological Chemistry 282, 56825690.

F. Glavan , I. Behm-Ansmant , E. Izaurralde & E. Conti (2006). Structures of the PIN domains of SMG6 and SMG5 reveal a nuclease within the mRNA surveillance complex. EMBO Journal 25, 51175125.

F. X. Gomis-Ruth & M. Coll (2006). Cut and move: protein machinery for DNA processing in bacterial conjugation. Current Opinion in Structural Biology 16, 744752.

M. A. Gorman , S. Morera , D. G. Rothwell , E. De La Fortelle , C. D. Mol , J. A. Tainer , I. D. Hickson & P. S. Freemont (1997). The crystal structure of the human DNA repair endonuclease HAP1 suggests the recognition of extra-helical deoxyribose at DNA abasic sites. EMBO Journal 16, 65486558.

E. B. Gottlin , A. E. Rudolph , Y. Zhao , H. R. Matthews & J. E. Dixon (1998). Catalytic mechanism of the phospholipase D superfamily proceeds via a covalent phosphohistidine intermediate. Proceedings of the National Academy of Sciences USA 95, 92029207.

M. Graille , L. Mora , R. H. Buckingham , H. Van Tilbeurgh & M. De Zamaroczy (2004). Structural inhibition of the colicin D tRNase by the tRNA-mimicking immunity protein. EMBO Journal 23, 14741482.

S. Grazulis , E. Manakova , M. Roessle , M. Bochtler , G. Tamulaitiene , R. Huber & V. Siksnys (2005). Structure of the metal-independent restriction enzyme BfiI reveals fusion of a specific DNA-binding domain with a nonspecific nuclease. Proceedings of the National Academy of Sciences USA 102, 1579715802.

J. P. Griffith , J. L. Kim , E. E. Kim , M. D. Sintchak , J. A. Thomson , M. J. Fitzgibbon , M. A. Fleming , P. R. Caron , K. Hsiao & M. A. Navia (1995). X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12–FK506 complex. Cell 82, 507522.

N. D. Grindley , K. L. Whiteson & P. A. Rice (2006). Mechanisms of site-specific recombination. Annual Review of Biochemistry 75, 567605.

C. Guerrier-Takada , K. Gardiner , T. Marsh , N. Pace & S. Altman (1983). The RNA moiety of ribonuclease P is the catalytic subunit of the enzyme. Cell 35, 849857.

F. Guo , D. N. Gopaul & G. D. Van Duyne (1997). Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse. Nature 389, 4046.

Y. Habraken , P. Sung , L. Prakash & S. Prakash (1993). Yeast excision repair gene RAD2 encodes a single-stranded DNA endonuclease. Nature 366, 365368.

J. M. Hadden , A.-C. Déclais , S. B. Carr , D. M. J. Lilley & E. V. Phillips (2007). The structural basis of Holliday junction resolution. Nature 449, 621624.

S. P. Hale , L. B. Poole & J. A. Gerlt (1993). Mechanism of the reaction catalyzed by staphylococcal nuclease: identification of the rate-determining step. Biochemistry 32, 74797487.

S. Hamdan , P. D. Carr , S. E. Brown , D. L. Ollis & N. E. Dixon (2002). Structural basis for proofreading during replication of the Escherichia coli chromosome. Structure 10, 535546.

M. M. Harding (1999). The geometry of metal-ligand interactions relevant to proteins. Acta Crystallographica D: Biological Crystallography 55, 14321443.

S. Hare , S. S. Gupta , E. Valkov , A. Engelman & P. Cherepanov (2010). Retroviral intasome assembly and inhibition of DNA strand transfer. Nature 464, 232236.

M. Haruki , Y. Tsunaka , M. Morikawa , S. Iwai & S. Kanaya (2000). Catalysis by Escherichia coli ribonuclease HI is facilitated by a phosphate group of the substrate. Biochemistry 39, 1393913944.

F. Hennecke , H. Kolmar , K. Brundl & H. J. Fritz (1991). The vsr gene product of E. coli K-12 is a strand- and sequence-specific DNA mismatch endonuclease. Nature 353, 776778.

M. Hernick & C. A. Fierke (2005). Zinc hydrolases: the mechanisms of zinc-dependent deacetylases. Archives of Biochemistry and Biophysics 433, 7184.

A. B. Hickman , Z. N. Perez , L. Zhou , P. Musingarimi , R. Ghirlando , J. E. Hinshaw , N. L. Craig & F. Dyda (2005). Molecular architecture of a eukaryotic DNA transposase. Nature Structural and Molecular Biology 12, 715721.

A. B. Hickman , D. R. Ronning , R. M. Kotin & F. Dyda (2002). Structural unity among viral origin binding proteins: crystal structure of the nuclease domain of adeno-associated virus Rep. Molecular Cell 10, 327337.

A. B. Hickman , D. R. Ronning , Z. N. Perez , R. M. Kotin & F. Dyda (2004). The nuclease domain of adeno-associated virus rep coordinates replication initiation using two distinct DNA recognition interfaces. Molecular Cell 13, 403414.

A. B. Hickman , S. Waninger , J. J. Scocca & F. Dyda (1997). Molecular organization in site-specific recombination: the catalytic domain of bacteriophage HP1 integrase at 2·7 A resolution. Cell 89, 227237.

D. E. Hoard & W. Goad (1968). Products in the initial stages of digestion of polydeoxynucleotides by pancreatic deoxyribonuclease (DNase I). Journal of Molecular Biology 31, 595606.

K. P. Hopfner , A. Karcher , L. Craig , T. T. Woo , J. P. Carney & J. A. Tainer (2001). Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase. Cell 105, 473485.

N. C. Horton (2008). DNA Nucleases. In Protein–Nucleic Acid Interactions (eds. P. A. Rice & C. C. Correll ), pp. 333363. Cambridge: Royal Society of Chemistry Publishing.

N. C. Horton & J. J. Perona (2004). DNA cleavage by EcoRV endonuclease: two metal ions in three metal ion binding sites. Biochemistry 43, 68416857.

E. Hough , L. K. Hansen , B. Birknes , K. Jynge , S. Hansen , A. Hordvik , C. Little , E. Dodson & Z. Derewenda (1989). High-resolution (1·5 A) crystal structure of phospholipase C from Bacillus cereus. Nature 338, 357360.

J. Houseley , J. Lacava & D. Tollervey (2006). RNA-quality control by the exosome. Nature Reviews Molecular Cell Biology 7, 529539.

K. C. Hsia , C. L. Li & H. S. Yuan (2005). Structural and functional insight into sugar-nonspecific nucleases in host defense. Current Opinion in Structural Biology 15, 126134.

Y. Y. Hsiao , A. Nakagawa , Z. Shi , S. Mitani , D. Xue & H. S. Yuan (2009). Crystal structure of CRN-4: implications for domain function in apoptotic DNA degradation. Molecular and Cellular Biology 29, 448457.

K. Y. Hwang , K. Baek , H. Y. Kim & Y. Cho (1998). The crystal structure of flap endonuclease-1 from Methanococcus jannaschii. Nature Structural Biology 5, 707713.

S. C. Ip , U. Rass , M. G. Blanco , H. R. Flynn , J. M. Skehel & S. C. West (2008). Identification of Holliday junction resolvases from humans and yeast. Nature 456, 357361.

M. Irie & K. Ohgi (2001). Ribonuclease T2. Methods in Enzymology 341, 4255.

R. Ishii , A. Minagawa , H. Takaku , M. Takagi , M. Nashimoto & S. Yokoyama (2005). Crystal structure of the tRNA 3′ processing endoribonuclease tRNase Z from Thermotoga maritima. Journal of Biological Chemistry 280, 1413814144.

K. Ishikawa , M. Watanabe , T. Kuroita , I. Uchiyama , J. M. Bujnicki , B. Kawakami , M. Tanokura & I. Kobayashi (2005). Discovery of a novel restriction endonuclease by genome comparison and application of a wheat-germ-based cell-free translation assay: PabI (5′-GTA/C) from the hyperthermophilic archaeon Pyrococcus abyssi. Nucleic Acids Research 33, e112.

I. Ivanov , J. A. Tainer & J. A. Mccammon (2007). Unraveling the three-metal-ion catalytic mechanism of the DNA repair enzyme endonuclease IV. Proceedings of the National Academy of Sciences USA 104, 14651470.

E. Jabri , M. B. Carr , R. P. Hausinger & P. A. Karplus (1995). The crystal structure of urease from Klebsiella aerogenes. Science 268, 9981004.

A. Jakubauskas , J. Giedriene , J. M. Bujnicki & A. Janulaitis (2007). Identification of a single HNH active site in type IIS restriction endonuclease Eco31I. Journal of Molecular Biology 370, 157169.

R. James , C. Kleanthous & G. R. Moore (1996). The biology of E colicins: paradigms and paradoxes. Microbiology 142, 15691580.

A. Jenny , L. Minvielle-Sebastia , P. J. Preker & W. Keller (1996). Sequence similarity between the 73-kilodalton protein of mammalian CPSF and a subunit of yeast polyadenylation factor I. Science 274, 15141517.

Y. Jin , G. Binkowski , L. D. Simon & D. Norris (1997). Ho endonuclease cleaves MAT DNA in vitro by an inefficient stoichiometric reaction mechanism. Journal of Biological Chemistry 272, 73527359.

E. R. Johnson & D. B. Mckay (1999). Mapping the role of active site residues for transducing an ATP-induced conformational change in the bovine 70-kDa heat shock cognate protein. Biochemistry 38, 1082310830.

S. J. Jones , A. F. Worrall & B. A. Connolly (1996). Site-directed mutagenesis of the catalytic residues of bovine pancreatic deoxyribonuclease I. Journal of Molecular Biology 264, 11541163.

A. T. Jonstrup , K. R. Andersen , L. B. Van & D. E. Brodersen (2007). The 1·4-A crystal structure of the S. pombe Pop2p deadenylase subunit unveils the configuration of an active enzyme. Nucleic Acids Research 35, 31533164.

L. Joshua-Tor (2006). The Argonautes. Cold Spring Harbor Symposia on Quantitative Biology 71, 6772.

F. A. Kadyrov , L. Dzantiev , N. Constantin & P. Modrich (2006). Endonucleolytic function of MutLalpha in human mismatch repair. Cell 126, 297308.

F. A. Kadyrov , S. F. Holmes , M. E. Arana , O. A. Lukianova , M. O'Donnell , T. A. Kunkel & P. Modrich (2007). Saccharomyces cerevisiae MutLalpha is a mismatch repair endonuclease. Journal of Biological Chemistry 282, 3718137190.

K. H. Kaminska , M. Kawai , M. Boniecki , I. Kobayashi & J. M. Bujnicki (2008). Type II restriction endonuclease R.Hpy188I belongs to the GIY-YIG nuclease superfamily, but exhibits an unusual active site. BMC Structural Biology 8, 48.

H. I. Kao & R. A. Bambara (2003). The protein components and mechanism of eukaryotic Okazaki fragment maturation. Critical Reviews in Biochemistry and Molecular Biology 38, 433452.

E. Karakas , J. J. Truglio , D. Croteau , B. Rhau , L. Wang , B. Van Houten & C. Kisker (2007). Structure of the C-terminal half of UvrC reveals an RNase H endonuclease domain with an Argonaute-like catalytic triad. EMBO Journal 26, 613622.

G. Kartha , J. Bello & D. Harker (1967). Tertiary structure of ribonuclease. Nature 213, 862865.

S. Kawano , Y. Kakuta , T. Nakashima & M. Kimura (2006). Crystal structures of the Nicotiana glutinosa ribonuclease NT in complex with nucleoside monophosphates. Journal of Biochemistry 140, 375381.

J. L. Keck , D. D. Roche , A. S. Lynch & J. M. Berger (2000). Structure of the RNA polymerase domain of E. coli primase. Science 287, 24822486.

S. Keeney (2001). Mechanism and control of meiotic recombination initiation. Current Topics in Developmental Biology 52, 153.

A. K. Kennedy , D. B. Haniford & K. Mizuuchi (2000). Single active site catalysis of the successive phosphoryl transfer steps by DNA transposases: insights from phosphorothioate stereoselectivity. Cell 101, 295305.

S. A. Khan (2005). Plasmid rolling-circle replication: highlights of two decades of research. Plasmid 53, 126136.

D. H. Kim & S. Mobashery (2001). Mechanism-based inhibition of zinc proteases. Current Medicinal Chemistry 8, 959965.

D. R. Kim , Y. Dai , C. L. Mundy , W. Yang & M. A. Oettinger (1999). Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinase. Genes and Development 13, 30703080.

E. E. Kim & H. W. Wyckoff (1991). Reaction mechanism of alkaline phosphatase based on crystal structures. Two-metal ion catalysis. Journal of Molecular Biology 218, 449464.

J. H. Kim , H. D. Kim , G. H. Ryu , D. H. Kim , J. Hurwitz & Y. S. Seo (2006). Isolation of human Dna2 endonuclease and characterization of its enzymatic properties. Nucleic Acids Research 34, 18541864.

Y. Kim , S. H. Eom , J. Wang , D. S. Lee , S. W. Suh & T. A. Steitz (1995). Crystal structure of Thermus aquaticus DNA polymerase. Nature 376, 612616.

L. A. Kirsebom (2007). RNase P RNA mediated cleavage: substrate recognition and catalysis. Biochimie 89, 11831194.

C. Kleanthous , U. C. Kuhlmann , A. J. Pommer , N. Ferguson , S. E. Radford , G. R. Moore , R. James & A. M. Hemmings (1999). Structural and mechanistic basis of immunity toward endonuclease colicins. Nature Structural Biology 6, 243252.

D. J. Klein & A. R. Ferre-D'amare (2006). Structural basis of glmS ribozyme activation by glucosamine-6-phosphate. Science 313, 17521756.

R. P. Klett , A. Cerami & E. Reich (1968). Exonuclease VI, a new nuclease activity associated with E. coli DNA polymerase. Proceedings of the National Academy of Sciences USA 60, 943950.

T. P. Ko , C. C. Liao , W. Y. Ku , K. F. Chak & H. S. Yuan (1999). The crystal structure of the DNase domain of colicin E7 in complex with its inhibitor Im7 protein. Structure 7, 91102.

B. Kobe & J. Deisenhofer (1996). Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A. Journal of Molecular Biology 264, 10281043.

O. O. Kolade , S. B. Carr , U. C. Kuhlmann , A. Pommer , C. Kleanthous , C. A. Bouchcinsky & A. M. Hemmings (2002). Structural aspects of the inhibition of DNase and rRNase colicins by their immunity proteins. Biochimie 84, 439446.

R. Kolodner , S. D. Hall & C. Luisi-Deluca (1994). Homologous pairing proteins encoded by the Escherichia coli recE and recT genes. Molecular Microbiology 11, 2330.

E. V. Koonin & T. V. Ilyina (1993). Computer-assisted dissection of rolling circle DNA replication. Biosystems 30, 241268.

J. Kosinski , G. Plotz , A. Guarne , J. M. Bujnicki & P. Friedhoff (2008). The PMS2 subunit of human MutLalpha contains a metal ion binding domain of the iron-dependent repressor protein family. Journal of Molecular Biology 382, 610627.

B. Kostelecky , E. Pohl , A. Vogel , O. Schilling & W. Meyer-Klaucke (2006). The crystal structure of the zinc phosphodiesterase from Escherichia coli provides insight into function and cooperativity of tRNase Z-family proteins. Journal of Bacteriology 188, 16071614.

R. Kovall & B. W. Matthews (1997). Toroidal structure of lambda-exonuclease. Science 277, 18241827.

K. Kruger , P. J. Grabowski , A. J. Zaug , J. Sands , D. E. Gottschling & T. R. Cech (1982). Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena. Cell 31, 147157.

U. C. Kuhlmann , G. R. Moore , R. James , C. Kleanthous & A. M. Hemmings (1999). Structural parsimony in endonuclease active sites: should the number of homing endonuclease families be redefined? FEBS Letters 463, 12.

M. Kunitz (1950). Crystalline desoxyribonuclease; isolation and general properties; spectrophotometric method for the measurement of desoxyribonuclease activity. Journal of General Physiology 33, 349362.

H. J. Kwon , R. Tirumalai , A. Landy & T. Ellenberger (1997). Flexibility in DNA recombination: structure of the lambda integrase catalytic core. Science 276, 126131.

P. Lagerback , E. Andersson , C. Malmberg & K. Carlson (2009). Bacteriophage T4 endonuclease II, a promiscuous GIY-YIG nuclease, binds as a tetramer to two DNA substrates. Nucleic Acids Research 37, 61746183.

A. Lagunavicius , G. Sasnauskas , S. E. Halford & V. Siksnys (2003). The metal-independent type IIs restriction enzyme BfiI is a dimer that binds two DNA sites but has only one catalytic centre. Journal of Molecular Biology 326, 10511064.

A. F. Lam , B. O. Krogh & L. S. Symington (2008). Unique and overlapping functions of the Exo1, Mre11 and Pso2 nucleases in DNA repair. DNA Repair (Amsterdam)7, 655662.

M. A. Landree , J. A. Wibbenmeyer & D. B. Roth (1999). Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombination. Genes and Development 13, 30593069.

P. Laneve , F. Altieri , M. E. Fiori , A. Scaloni , I. Bozzoni & E. Caffarelli (2003). Purification, cloning, and characterization of XendoU, a novel endoribonuclease involved in processing of intron-encoded small nucleolar RNAs in Xenopus laevis. Journal of Biological Chemistry 278, 1302613032.

P. Laneve , U. Gioia , R. Ragno , F. Altieri , C. Di Franco , T. Santini , M. Arceci , I. Bozzoni & E. Caffarelli (2008). The tumor marker human placental protein 11 is an endoribonuclease. Journal of Biological Chemistry 283, 3471234719.

S. J. Lange & L. Que JR. ( 1998). Oxygen activating nonheme iron enzymes. Current Opinion in Chemical Biology 2, 159172.

M. Lapkouski , S. Panjikar , P. Janscak , I. K. Smatanova , J. Carey , R. Ettrich & E. Csefalvay (2009). Structure of the motor subunit of type I restriction–modification complex EcoR124I. Nature Structural and Molecular Biology 16, 9495.

C. Larkin , S. Datta , M. J. Harley , B. J. Anderson , A. Ebie , V. Hargreaves & J. F. Schildbach (2005). Inter- and intramolecular determinants of the specificity of single-stranded DNA binding and cleavage by the F factor relaxase. Structure 13, 15331544.

C. Larkin , R. J. Haft , M. J. Harley , B. Traxler & J. F. Schildbach (2007). Roles of active site residues and the HUH motif of the F plasmid TraI relaxase. Journal of Biological Chemistry 282, 3370733713.

B. I. Lee , K. H. Kim , S. J. Park , S. H. Eom , H. K. Song & S. W. Suh (2004). Ring-shaped architecture of RecR: implications for its role in homologous recombinational DNA repair. EMBO Journal 23, 20292038.

B. I. Lee & D. M. Wilson 3RD. (1999). The RAD2 domain of human exonuclease 1 exhibits 5′ to 3′ exonuclease and flap structure-specific endonuclease activities. Journal of Biological Chemistry 274, 3776337769.

F. S. Lee , D. S. Auld & B. L. Vallee (1989). Tryptophan fluorescence as a probe of placental ribonuclease inhibitor binding to angiogenin. Biochemistry 28, 219224.

J. Y. Lee , J. Chang , N. Joseph , R. Ghirlando , D. N. Rao & W. Yang (2005). MutH complexed with Hemi- and unmethylated DNAs: coupling base recognition and DNA cleavage. Molecular Cell 20, 155166.

K. P. Lee , M. Dey , D. Neculai , C. Cao , T. E. Dever & F. Sicheri (2008). Structure of the dual enzyme Ire1 reveals the basis for catalysis and regulation in nonconventional RNA splicing. Cell 132, 89100.

G. M. Li (2008). Mechanisms and functions of DNA mismatch repair. Cell Research 18, 8598.

W. Li , S. Kamtekar , Y. Xiong , G. J. Sarkis , N. D. Grindley & T. A. Steitz (2005). Structure of a synaptic gammadelta resolvase tetramer covalently linked to two cleaved DNAs. Science 309, 12101215.

D. M. Lilley (2005). Structure, folding and mechanisms of ribozymes. Current Opinion in Structural Biology 15, 313323.

D. M. Lilley & M. F. White (2001). The junction-resolving enzymes. Nature Reviews Molecular Cell Biology 2, 433443.

Q. Liu , J. C. Greimann & C. D. Lima (2006). Reconstitution, activities, and structure of the eukaryotic RNA exosome. Cell 127, 12231237.

X. Liu , H. Zou , C. Slaughter & X. Wang (1997). DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis. Cell 89, 175184.

Y. Liu , H. I. Kao & R. A. Bambara (2004). Flap endonuclease 1: a central component of DNA metabolism. Annual Review of Biochemistry 73, 589615.

M. Llosa , F. X. Gomis-Ruth , M. Coll & F. De La Cruz Fd (2002). Bacterial conjugation: a two-step mechanism for DNA transport. Molecular Microbiology 45, 18.

P. J. Loll , S. Quirk , E. E. Lattman & R. M. Garavito (1995). X-ray crystal structures of staphylococcal nuclease complexed with the competitive inhibitor cobalt(II) and nucleotide. Biochemistry 34, 43164324.

E. Lorentzen , J. Basquin , R. Tomecki , A. Dziembowski & E. Conti (2008). Structure of the active subunit of the yeast exosome core, Rrp44: diverse modes of substrate recruitment in the RNase II nuclease family. Molecular Cell 29, 717728.

E. Lorentzen , A. Dziembowski , D. Lindner , B. Seraphin & E. Conti (2007). RNA channelling by the archaeal exosome. EMBO Reports 8, 470476.

E. Lorentzen , P. Walter , S. Fribourg , E. Evguenieva-Hackenberg , G. Klug & E. Conti (2005). The archaeal exosome core is a hexameric ring structure with three catalytic subunits. Nature Structural and Molecular Biology 12, 575581.

V. Lyamichev , M. A. Brow & J. E. Dahlberg (1993). Structure-specific endonucleolytic cleavage of nucleic acids by eubacterial DNA polymerases. Science 260, 778783.

S. Lykke-Andersen , D. E. Brodersen & T. H. Jensen (2009). Origins and activities of the eukaryotic exosome. Journal of Cell Science 122, 14871494.

C. Macelrevey , J. D. Salter , J. Krucinska & J. E. Wedekind (2008). Structural effects of nucleobase variations at key active site residue Ade38 in the hairpin ribozyme. RNA 14, 16001616.

R. Macmaster , S. Sedelnikova , P. J. Baker , E. L. Bolt , R. G. Lloyd & J. B. Rafferty (2006). RusA Holliday junction resolvase: DNA complex structure – insights into selectivity and specificity. Nucleic Acids Research 34, 55775584.

I. J. Macrae & J. A. Doudna (2007). Ribonuclease revisited: structural insights into ribonuclease III family enzymes. Current Opinion in Structural Biology 17, 138145.

I. J. Macrae , K. Zhou & J. A. Doudna (2007). Structural determinants of RNA recognition and cleavage by Dicer. Nature Structural and Molecular Biology 14, 934940.

I. J. Macrae , K. Zhou , F. Li , A. Repic , A. N. Brooks , W. Z. Cande , P. D. Adams & J. A. Doudna (2006). Structural basis for double-stranded RNA processing by Dicer. Science 311, 195198.

M. E. Maguire & J. A. Cowan (2002). Magnesium chemistry and biochemistry. Biometals 15, 203210.

K. S. Makarova , N. V. Grishin , S. A. Shabalina , Y. I. Wolf & E. V. Koonin (2006). A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action. Biology Direct 1, 7.

C. R. Mandel , S. Kaneko , H. Zhang , D. Gebauer , V. Vethantham , J. L. Manley & L. Tong (2006). Polyadenylation factor CPSF-73 is the pre-mRNA 3′-end-processing endonuclease. Nature 444, 953956.

T. M. Marti & O. Fleck (2004). DNA repair nucleases. Cellular and Molecular Life Science 61, 336354.

F. Martinez Valle , E. Balada , J. Ordi-Ros & M. Vilardell-Tarres (2008). DNase 1 and systemic lupus erythematosus. Autoimmunity Reviews 7, 359363.

W. F. Marzluff , E. J. Wagner & R. J. Duronio (2008). Metabolism and regulation of canonical histone mRNAs: life without a poly(A) tail. Nature Reviews Genetics 9, 843854.

T. Masuda-Sasa , O. Imamura & J. L. Campbell (2006). Biochemical analysis of human Dna2. Nucleic Acids Research 34, 18651875.

M. J. Mate & C. Kleanthous (2004). Structure-based analysis of the metal-dependent mechanism of H-N-H endonucleases. Journal of Biological Chemistry 279, 3476334769.

L. Mazzarella , S. Capasso , D. Demasi , G. Di Lorenzo , C. A. Mattia & A. Zagari (1993). Bovine seminal ribonuclease: structure at 1·9 A resolution. Acta Crystallographica D: Biological Crystallography 49, 389402.

C. S. Mchenry (1985). DNA polymerase III holoenzyme of Escherichia coli: components and function of a true replicative complex. Molecular and Cellular Biochemistry 66, 7185.

A. Merlino , C. Ercole , D. Picone , E. Pizzo , L. Mazzarella & F. Sica (2008). The buried diversity of bovine seminal ribonuclease: shape and cytotoxicity of the swapped non-covalent form of the enzyme. Journal of Molecular Biology 376, 427437.

F. Michel , M. Costa & E. Westhof (2009). The ribozyme core of group II introns: a structure in want of partners. Trends in Biochemical Sciences 34, 189199.

S. F. Midtgaard , J. Assenholt , A. T. Jonstrup , L. B. Van , T. H. Jensen & D. E. Brodersen (2006). Structure of the nuclear exosome component Rrp6p reveals an interplay between the active site and the HRDC domain. Proceedings of the National Academy of Sciences USA 103, 1189811903.

A. S. Mildvan , Z. Xia , H. F. Azurmendi , V. Saraswat , P. M. Legler , M. A. Massiah , S. B. Gabelli , M. A. Bianchet , L. W. Kang & L. M. Amzel (2005). Structures and mechanisms of Nudix hydrolases. Archives of Biochemistry and Biophysics 433, 129143.

E. P. Mimitou & L. S. Symington (2009). DNA end resection: many nucleases make light work. DNA Repair (Amsterdam) 8, 983995.

A. Minagawa , H. Takaku , M. Takagi & M. Nashimoto (2004). A novel endonucleolytic mechanism to generate the CCA 3′ termini of tRNA molecules in Thermotoga maritima. Journal of Biological Chemistry 279, 1568815697.

K. Miyazono , M. Watanabe , J. Kosinski , K. Ishikawa , M. Kamo , T. Sawasaki , K. Nagata , J. M. Bujnicki , Y. Endo , M. Tanokura & I. Kobayashi (2007). Novel protein fold discovered in the PabI family of restriction enzymes. Nucleic Acids Research 35, 19081918.

C. D. Mol , C. F. Kuo , M. M. Thayer , R. P. Cunningham & J. A. Tainer (1995). Structure and function of the multifunctional DNA-repair enzyme exonuclease III. Nature 374, 381386.

A. F. Monzingo , A. Ozburn , S. Xia , R. J. Meyer & J. D. Robertus (2007). The structure of the minimal relaxase domain of MobA at 2·1 A resolution. Journal of Molecular Biology 366, 165178.

M. J. Moore & N. J. Proudfoot (2009). Pre-mRNA processing reaches back to transcription and ahead to translation. Cell 136, 688700.

M. Morita , G. Stamp , P. Robins , A. Dulic , I. Rosewell , G. Hrivnak , G. Daly , T. Lindahl & D. E. Barnes (2004). Gene-targeted mice lacking the Trex1 (DNase III) 3′→5′ DNA exonuclease develop inflammatory myocarditis. Molecular and Cellular Biology 24, 67196727.

D. Moshous , I. Callebaut , R. De Chasseval , B. Corneo , M. Cavazzana-Calvo , F. Le Deist , I. Tezcan , O. Sanal , Y. Bertrand , N. Philippe , A. Fischer & J. P. De Villartay (2001). Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency. Cell 105, 177186.

C. M. Moure , F. S. Gimble & F. A. Quiocho (2008). Crystal structures of I-SceI complexed to nicked DNA substrates: snapshots of intermediates along the DNA cleavage reaction pathway. Nucleic Acids Research 36, 32873296.

M. Muftuoglu , J. Oshima , C. Von Kobbe , W. H. Cheng , D. F. Leistritz & V. A. Bohr (2008). The clinical characteristics of Werner syndrome: molecular and biochemical diagnosis. Human Genetics 124, 369377.

A. M. Muro-Pastor , E. Flores , A. Herrero & C. P. Wolk (1992). Identification, genetic analysis and characterization of a sugar-non-specific nuclease from the cyanobacterium Anabaena sp. PCC 7120. Molecular Microbiology 6, 30213030.

N. E. Murray (2000). Type I restriction systems: sophisticated molecular machines (a legacy of Bertani and Weigle). Microbiology and Molecular Biology Reviews 64, 412434.

S. Nagata (2007). Autoimmune diseases caused by defects in clearing dead cells and nuclei expelled from erythroid precursors. Immunological Reviews 220, 237250.

J. Nandakumar , B. Schwer , R. Schaffrath & S. Shuman (2008). RNA repair: an antidote to cytotoxic eukaryal RNA damage. Molecular Cell 31, 278286.

M. Newman , K. Lunnen , G. Wilson , J. Greci , I. Schildkraut & S. E. Phillips (1998). Crystal structure of restriction endonuclease BglI bound to its interrupted DNA recognition sequence. EMBO Journal 17, 54665476.

M. Newman , J. Murray-Rust , J. Lally , J. Rudolf , A. Fadden , P. P. Knowles , M. F. White & N. Q. Mcdonald (2005). Structure of an XPF endonuclease with and without DNA suggests a model for substrate recognition. EMBO Journal 24, 895905.

M. D. Nichols , K. Deangelis , J. L. Keck & J. M. Berger (1999). Structure and function of an archaeal topoisomerase VI subunit with homology to the meiotic recombination factor Spo11. EMBO Journal 18, 61776188.

T. Nishino , K. Komori , Y. Ishino & K. Morikawa (2003). X-ray and biochemical anatomy of an archaeal XPF/Rad1/Mus81 family nuclease: similarity between its endonuclease domain and restriction enzymes. Structure 11, 445457.

M. Y. Niv , D. R. Ripoll , J. A. Vila , A. Liwo , E. S. Vanamee , A. K. Aggarwal , H. Weinstein & H. A. Scheraga (2007). Topology of Type II REases revisited; structural classes and the common conserved core. Nucleic Acids Research 35, 22272237.

M. Nowotny (2009). Retroviral integrase superfamily: the structural perspective. EMBO Reports 10, 144151.

M. Nowotny , S. M. Cerritelli , R. Ghirlando , S. A. Gaidamakov , R. J. Crouch & W. Yang (2008). Specific recognition of RNA/DNA hybrid and enhancement of human RNase H1 activity by HBD. EMBO Journal 27, 11721181.

M. Nowotny , S. A. Gaidamakov , R. J. Crouch & W. Yang (2005). Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis. Cell 121, 10051016.

M. Nowotny , S. A. Gaidamakov , R. Ghirlando , S. M. Cerritelli , R. J. Crouch & W. Yang (2007). Structure of human RNase H1 complexed with an RNA/DNA hybrid: insight into HIV reverse transcription. Molecular Cell 28, 264276.

M. Nowotny & W. Yang (2006). Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release. EMBO Journal 25, 19241933.

A. O'DONOVAN , A. A. Davies , J. G. Moggs , S. C. West & R. D. Wood (1994). XPG endonuclease makes the 3′ incision in human DNA nucleotide excision repair. Nature 371, 432435.

D. L. Ollis , P. Brick , R. Hamlin , N. G. Xuong & T. A. Steitz (1985). Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP. Nature 313, 762766.

N. Olmo , J. Turnay , G. Gonzalez De Buitrago , I. Lopez De Silanes , J. G. Gavilanes & M. A. Lizarbe (2001). Cytotoxic mechanism of the ribotoxin alpha-sarcin. Induction of cell death via apoptosis. European Journal of Biochemistry 268, 21132123.

J. Orlowski & J. M. Bujnicki (2008). Structural and evolutionary classification of type II restriction enzymes based on theoretical and experimental analyses. Nucleic Acids Research 36, 35523569.

C. Q. Pan & R. A. Lazarus (1999). Ca2+-dependent activity of human DNase I and its hyperactive variants. Protein Science 8, 17801788.

B. Paquin , C. J. O'KELLY & B. F. Lang (1995). Intron-encoded open reading frame of the GIY-YIG subclass in a plastid gene. Current Genetics 28, 9799.

R. Parker & H. Song (2004). The enzymes and control of eukaryotic mRNA turnover. Nature Structural and Molecular Biology 11, 121127.

J. Z. Parrish & D. Xue (2006). Cuts can kill: the roles of apoptotic nucleases in cell death and animal development. Chromosoma 115, 8997.

A. A. Patel & J. A. Steitz (2003). Splicing double: insights from the second spliceosome. Nature Reviews Molecular Cell Biology 4, 960970.

T. T. Paull & M. Gellert (1998). The 3′ to 5′ exonuclease activity of Mre 11 facilitates repair of DNA double-strand breaks. Molecular Cell 1, 969979.

T. T. Paull & M. Gellert (1999). Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex. Genes and Development 13, 12761288.

C. L. Peebles , P. S. Perlman , K. L. Mecklenburg , M. L. Petrillo , J. H. Tabor , K. A. Jarrell & H. L. Cheng (1986). A self-splicing RNA excises an intron lariat. Cell 44, 213223.

V. Pena , A. Rozov , P. Fabrizio , R. Luhrmann & M. C. Wahl (2008). Structure and function of an RNase H domain at the heart of the spliceosome. EMBO Journal 27, 29292940.

F. W. Perrino , S. Harvey , S. Mcmillin & T. Hollis (2005). The human TREX2 3′→5′-exonuclease structure suggests a mechanism for efficient nonprocessive DNA catalysis. Journal of Biological Chemistry 280, 1521215218.

J. J. Perry , S. M. Yannone , L. G. Holden , C. Hitomi , A. Asaithamby , S. Han , P. K. Cooper , D. J. Chen & J. A. Tainer (2006a). WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing. Nature Structural and Molecular Biology 13, 414422.

K. Perry , Y. Hwang , F. D. Bushman & G. D. Van Duyne (2006b). Structural basis for specificity in the poxvirus topoisomerase. Molecular Cell 23, 343354.

E. Pidcock & G. R. Moore (2001). Structural characteristics of protein binding sites for calcium and lanthanide ions. Journal of Biology and Inorganic Chemistry 6, 479489.

A. Pingoud , M. Fuxreiter , V. Pingoud & W. Wende (2005). Type II restriction endonucleases: structure and mechanism. Cellular and Molecular Life Science 62, 685707.

V. Pingoud , W. Wende , P. Friedhoff , M. Reuter , J. Alves , A. Jeltsch , L. Mones , M. Fuxreiter & A. Pingoud (2009). On the divalent metal ion dependence of DNA cleavage by restriction endonucleases of the EcoRI family. Journal of Molecular Biology 393, 140160.

B. W. Pontius , W. B. Lott & P. H. Von Hippel (1997). Observations on catalysis by hammerhead ribozymes are consistent with a two-divalent-metal-ion mechanism. Proceedings of the National Academy of Sciences USA 94, 22902294.

J. J. Pouliot , K. C. Yao , C. A. Robertson & H. A. Nash (1999). Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes. Science 286, 552555.

J. B. Rafferty , E. L. Bolt , T. A. Muranova , S. E. Sedelnikova , P. Leonard , A. Pasquo , P. J. Baker , D. W. Rice , G. J. Sharples & R. G. Lloyd (2003). The structure of Escherichia coli RusA endonuclease reveals a new Holliday junction DNA binding fold. Structure 11, 15571567.

R. T. Raines (1998). Ribonuclease A. Chem Rev 98, 10451066.

E. S. Rangarajan & V. Shankar (2001). Sugar non-specific endonucleases. FEMS Microbiology Reviews 25, 583613.

M. R. Redinbo , J. J. Champoux & W. G. Hol (2000). Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA. Biochemistry 39, 68326840.

M. R. Redinbo , L. Stewart , P. Kuhn , J. J. Champoux & W. G. Hol (1998). Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA. Science 279, 15041513.

R. R. Reed (1981). Transposon-mediated site-specific recombination: a defined in vitro system. Cell 25, 713719.

L. J. Reha-Krantz (2010). DNA polymerase proofreading: multiple roles maintain genome stability. Biochimica et Biophysica Acta 1804, 10491063.

T. A. Reiter , N. J. Reiter & F. Rusnak (2002). Mn2+ is a native metal ion activator for bacteriophage lambda protein phosphatase. Biochemistry 41, 1540415409.

F. Renzi , E. Caffarelli , P. Laneve , I. Bozzoni , M. Brunori & B. Vallone (2006). The structure of the endoribonuclease XendoU: From small nucleolar RNA processing to severe acute respiratory syndrome coronavirus replication. Proceedings of the National Academy of Sciences USA 103, 1236512370.

P. Rice & K. Mizuuchi (1995). Structure of the bacteriophage Mu transposase core: a common structural motif for DNA transposition and retroviral integration. Cell 82, 209220.

J. M. Richardson , S. D. Colloms , D. J. Finnegan & M. D. Walkinshaw (2009). Molecular architecture of the Mos1 paired-end complex: the structural basis of DNA transposition in a eukaryote. Cell 138, 10961108.

D. B. Ritchie , M. J. Schellenberg , E. M. Gesner , S. A. Raithatha , D. T. Stuart & A. M. Macmillan (2008). Structural elucidation of a PRP8 core domain from the heart of the spliceosome. Nature Structural and Molecular Biology 15, 11991205.

R. J. Roberts , T. Vincze , J. Posfai & D. Macelis (2009). REBASE – a database for DNA restriction and modification: enzymes, genes and genomes. Nucleic Acids Research 38 (Database Issue), D234236.

A. Romani & A. Scarpa (1992). Regulation of cell magnesium. Archives of Biochemistry and Biophysics 298, 112.

C. Romier , R. Dominguez , A. Lahm , O. Dahl & D. Suck (1998). Recognition of single-stranded DNA by nuclease P1: high resolution crystal structures of complexes with substrate analogs. Proteins 32, 414424.

P. B. Rupert , A. P. Massey , S. T. Sigurdsson & A. R. Ferre-D'amare (2002). Transition state stabilization by a catalytic RNA. Science 298, 14211424.

T. J. Rutkoski & R. T. Raines (2008). Evasion of ribonuclease inhibitor as a determinant of ribonuclease cytotoxicity. Current Pharmaceutical Biotechnology 9, 185189.

K. Ryan , O. Calvo & J. L. Manley (2004). Evidence that polyadenylation factor CPSF-73 is the mRNA 3′ processing endonuclease. RNA 10, 565573.

W. Saenger (1984). Principles of Nucleic Acid Structure, New York, NY: Springer.

M. D. Sam & J. J. Perona (1999). Catalytic roles of divalent metal ions in phosphoryl transfer by EcoRV endonuclease. Biochemistry 38, 65766586.

G. Sasnauskas , B. A. Connolly , S. E. Halford & V. Siksnys (2007). Site-specific DNA transesterification catalyzed by a restriction enzyme. Proceedings of the National Academy of Sciences USA 104, 21152120.

G. Sasnauskas , L. Zakrys , M. Zaremba , R. Cosstick , J. W. Gaynor , S. E. Halford & V. Siksnys (2010). A novel mechanism for the scission of double-stranded DNA: BfiI cuts both 3′–5′ and 5′–3′ strands by rotating a single active site. Nucleic Acids Research 38, 23992410.

D. Scherly , T. Nouspikel , J. Corlet , C. Ucla , A. Bairoch & S. G. Clarkson (1993). Complementation of the DNA repair defect in xeroderma pigmentosum group G cells by a human cDNA related to yeast RAD2. Nature 363, 182185.

S. Schiffer , S. Rosch & A. Marchfelder (2002). Assigning a function to a conserved group of proteins: the tRNA 3′-processing enzymes. EMBO Journal 21, 27692777.

A. A. Schulga , K. M. Nurkiyanova , V. M. Zakharyev , M. P. Kirpichnikov & K. G. Skryabin (1992). Cloning of the gene encoding RNase binase from Bacillus intermedius 7P. Nucleic Acids Research 20, 2375.

S. C. Schuster , W. Miller , A. Ratan , L. P. Tomsho , B. Giardine , L. R. Kasson , R. S. Harris , D. C. Petersen , F. Zhao , J. Qi , C. Alkan , J. M. Kidd , Y. Sun , D. I. Drautz , P. Bouffard , D. M. Muzny , J. G. Reid , L. V. Nazareth , Q. Wang , R. Burhans , C. Riemer , N. E. Wittekindt , P. Moorjani , E. A. Tindall , C. G. Danko , W. S. Teo , A. M. Buboltz , Z. Zhang , Q. Ma , A. Oosthuysen , A. W. Steenkamp , H. Oostuisen , P. Venter , J. Gajewski , Y. Zhang , B. F. Pugh , K. D. Makova , A. Nekrutenko , E. R. Mardis , N. Patterson , T. H. Pringle , F. Chiaromonte , J. C. Mullikin , E. E. Eichler , R. C. Hardison , R. A. Gibbs , T. T. Harkins & V. M. Hayes (2010). Complete Khoisan and Bantu genomes from southern Africa. Nature 463, 943947.

W. G. Scott , J. B. Murray , J. R. Arnold , B. L. Stoddard & A. Klug (1996). Capturing the structure of a catalytic RNA intermediate: the hammerhead ribozyme. Science 274, 20652069.

S. Sharma , J. A. Sommers , H. C. Driscoll , L. Uzdilla , T. M. Wilson & R. M. Brosh JR. (2003). The exonucleolytic and endonucleolytic cleavage activities of human exonuclease 1 are stimulated by an interaction with the carboxyl-terminal region of the Werner syndrome protein. Journal of Biological Chemistry 278, 2348723496.

B. Shen , P. Singh , R. Liu , J. Qiu , L. Zheng , L. D. Finger & S. Alas (2005). Multiple but dissectible functions of FEN-1 nucleases in nucleic acid processing, genome stability and diseases. Bioessays 27, 717729.

I. V. Shevelev , K. Ramadan & U. Hubscher (2002). The TREX2 3′→5′ exonuclease physically interacts with DNA polymerase delta and increases its accuracy. ScientificWorld Journal 2, 275281.