Abstract
Endonuclease V (endo V) was first discovered as the fifth endonuclease in Escherichia coli in 1977 and later rediscovered as a deoxyinosine 3′ endonuclease. Decades of biochemical and genetic investigations have accumulated rich information on its role as a DNA repair enzyme for the removal of deaminated bases. Structural and biochemical analyses have offered invaluable insights on its recognition capacity, catalytic mechanism, and multitude of enzymatic activities. The roles of endo V in genome maintenance have been validated in both prokaryotic and eukaryotic organisms. The ubiquitous nature of endo V in the three domains of life: Bacteria, Archaea, and Eukaryotes, indicates its existence in the early evolutionary stage of cellular life. The application of endo V in mutation detection and DNA manipulation underscores its value beyond cellular DNA repair. This review is intended to provide a comprehensive account of the historic aspects, biochemical, structural biological, genetic and biotechnological studies of this unusual DNA repair enzyme.
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References
Burney S, Caulfield JL, Niles JC, Wishnok JS, Tannenbaum SR (1999) The chemistry of DNA damage from nitric oxide and peroxynitrite. Mutat Res 424:37–49
Dedon PC, Tannenbaum SR (2004) Reactive nitrogen species in the chemical biology of inflammation. Arch Biochem Biophys 423:12–22
Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362:709–715
Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR (1992) DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 89:3030–3034
Shapiro R (1981) Damage to DNA caused by hydrolysis. In: Seeberg E, Kleppe K (eds) Chromosome damage and repair. Plenum Press, New York, pp 3–18
Spencer JP, Whiteman M, Jenner A, Halliwell B (2000) Nitrite-induced deamination and hypochlorite-induced oxidation of DNA in intact human respiratory tract epithelial cells. Free Radic Biol Med 28:1039–1050
Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra M, Dunams TM, Cebula TA, Koch WH, Andrews AW, Allen JS et al (1991) DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science 254:1001–1003
Suzuki T, Yamaoka R, Nishi M, Ide H, Makino K (1996) Isolation and characterization of a novel product, 2′-deoxyoxanosine, from 2′-deoxyguanosine, oligodeoxynucleotide and calf thymus DNA treated by nitrous-acid and nitric-oxide. J Am Chem Soc 118:2515–2516
Parikh SS, Putnam CD, Tainer JA (2000) Lessons learned from structural results on uracil-DNA glycosylase. Mutat Res 460:183–199
Pearl LH (2000) Structure and function in the uracil-DNA glycosylase superfamily. Mutat Res 460:165–181
Mi R, Dong L, Kaulgud T, Hackett KW, Dominy BN, Cao W (2009) Insights from xanthine and uracil DNA glycosylase activities of bacterial and human SMUG1: switching SMUG1 to UDG. J Mol Biol 385:761–778
Lee HW, Brice AR, Wright CB, Dominy BN, Cao W (2010) Identification of Escherichia coli mismatch-specific uracil DNA glycosylase as a robust xanthine DNA glycosylase. J Biol Chem 285:41483–41490
Lee HW, Dominy BN, Cao W (2011) New family of deamination repair enzymes in uracil-DNA glycosylase superfamily. J Biol Chem 286:31282–31287
Dong L, Meira LB, Hazra TK, Samson LD, Cao W (2008) Oxanine DNA glycosylase activities in mammalian systems. DNA Repair 7:128–134
Dong L, Mi R, Glass RA, Barry JN, Cao W (2008) Repair of deaminated base damage by Schizosaccharomyces pombe thymine DNA glycosylase. DNA Repair 7:1962–1972
Hitchcock TM, Dong L, Connor EE, Meira LB, Samson LD, Wyatt MD, Cao W (2004) Oxanine DNA glycosylase activity from mammalian alkyladenine glycosylase. J Biol Chem 279:38177–38183
Saparbaev M, Laval J (1994) Excision of hypoxanthine from DNA containing dIMP residues by the Escherichia coli, yeast, rat, and human alkylpurine DNA glycosylases. Proc Natl Acad Sci USA 91:5873–5877
Terato H, Masaoka A, Asagoshi K, Honsho A, Ohyama Y, Suzuki T, Yamada M, Makino K, Yamamoto K, Ide H (2002) Novel repair activities of AlkA (3-methyladenine DNA glycosylase II) and endonuclease VIII for xanthine and oxanine, guanine lesions induced by nitric oxide and nitrous acid. Nucleic Acids Res 30:4975–4984
Cortazar D, Kunz C, Saito Y, Steinacher R, Schar P (2007) The enigmatic thymine DNA glycosylase. DNA Repair 6:489–504
Kow YW (2002) Repair of deaminated bases in DNA. Free Radic Biol Med 33:886–893
Krokan HE, Drablos F, Slupphaug G (2002) Uracil in DNA—occurrence, consequences and repair. Oncogene 21:8935–8948
Dalhus B, Laerdahl JK, Backe PH, Bjoras M (2009) DNA base repair–recognition and initiation of catalysis. FEMS Microbiol Rev 33:1044–1078
Barnes DE, Lindahl T (2004) Repair and genetic consequences of endogenous DNA base damage in mammalian cells. Annu Rev Genet 38:445–476
Stivers JT, Jiang YL (2003) A mechanistic perspective on the chemistry of DNA repair glycosylases. Chem Rev 103:2729–2759
Gates FT 3rd, Linn S (1977) Endonuclease V of Escherichia coli. J Biol Chem 252:1647–1653
Linn S (2012) Life in the serendipitous lane: excitement and gratification in studying DNA repair. DNA Repair 11:595–605
Demple B, Linn S (1982) On the recognition and cleavage mechanism of Escherichia coli endodeoxyribonuclease V, a possible DNA repair enzyme. J Biol Chem 257:2848–2855
Harosh I, Sperling J (1988) Hypoxanthine-DNA glycosylase from Escherichia coli. Partial purification and properties. J Biol Chem 263:3328–3334
Karran P, Lindahl T (1978) Enzymatic excision of free hypoxanthine from polydeoxynucleotides and DNA containing deoxyinosine monophosphate residues. J Biol Chem 253:5877–5879
Yao M, Hatahet Z, Melamede RJ, Kow YW (1994) Purification and characterization of a novel deoxyinosine-specific enzyme, deoxyinosine 3′ endonuclease, from Escherichia coli. J Biol Chem 269:16260–16268
Yao M, Kow YW (1994) Strand-specific cleavage of mismatch-containing DNA by deoxyinosine 3′-endonuclease from Escherichia coli. J Biol Chem 269:31390–31396
Yao M, Kow YW (1995) Interaction of deoxyinosine 3′-endonuclease from Escherichia coli with DNA containing deoxyinosine. J Biol Chem 270:28609–28616
Yao M, Kow YW (1996) Cleavage of insertion/deletion mismatches, flap and pseudo-Y DNA structures by deoxyinosine 3′-endonuclease from Escherichia coli. J Biol Chem 271:30672–30676
Yao M, Kow YW (1997) Further characterization of Escherichia coli endonuclease V. J Biol Chem 272:30774–30779
Demple B, Gates FT, 3rd, Linn S (1980) Purification and properties of Escherichia coli endodeoxyribonuclease V. Methods Enzymol 65:224–231
Guo G, Ding Y, Weiss B (1997) nfi, the gene for endonuclease V in Escherichia coli K-12. J Bacteriol 179:310–316
Dianov G, Lindahl T (1991) Preferential recognition of I.T base-pairs in the initiation of excision-repair by hypoxanthine-DNA glycosylase. Nucleic Acids Res 19:3829–3833
Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T (2006) DNA repair and mutagenesis, 2nd edn. ASM Press, Washington, DC
Sekiguchi M (2012) My path toward DNA repair. DNA Repair 11:606–615
Yasuda S, Sekiguchi M (1970) T4 endonuclease involved in repair of DNA. Proc Natl Acad Sci USA 67:1839–1845
Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, Boursnell C, Pang N, Forslund K, Ceric G, Clements J, Heger A, Holm L, Sonnhammer EL, Eddy SR, Bateman A, Finn RD (2012) The Pfam protein families database. Nucleic Acids Res 40:D290–301
Aravind L, Walker DR, Koonin EV (1999) Conserved domains in DNA repair proteins and evolution of repair systems. Nucleic Acids Res 27:1223–1242
Van Houten B, Croteau DL, DellaVecchia MJ, Wang H, Kisker C (2005) ‘Close-fitting sleeves’: DNA damage recognition by the UvrABC nuclease system. Mutat Res 577:92–117
Nowotny M (2009) Retroviral integrase superfamily: the structural perspective. EMBO Rep 10:144–151
Haren L, Ton-Hoang B, Chandler M (1999) Integrating DNA: transposases and retroviral integrases. Annu Rev Microbiol 53:245–281
Rand TA, Ginalski K, Grishin NV, Wang X (2004) Biochemical identification of Argonaute 2 as the sole protein required for RNA-induced silencing complex activity. Proc Natl Acad Sci USA 101:14385–14389
Song JJ, Smith SK, Hannon GJ, Joshua-Tor L (2004) Crystal structure of Argonaute and its implications for RISC slicer activity. Science 305:1434–1437
Majorek KA, Bujnicki JM (2009) Modeling of Escherichia coli endonuclease V structure in complex with DNA. J Mol Model 15:173–182
Dalhus B, Arvai AS, Rosnes I, Olsen OE, Backe PH, Alseth I, Gao H, Cao W, Tainer JA, Bjoras M (2009) Structures of endonuclease V with DNA reveal initiation of deaminated adenine repair. Nat Struct Mol Biol 16:138–143
Huffman JL, Sundheim O, Tainer JA (2005) DNA base damage recognition and removal: new twists and grooves. Mutat Res 577:55–76
Roberts RJ, Cheng X (1998) Base flipping. Annu Rev Biochem 67:181–198
Scharer OD, Campbell AJ (2009) Wedging out DNA damage. Nat Struct Mol Biol 16:102–104
Huang J, Lu J, Barany F, Cao W (2001) Multiple cleavage activities of endonuclease V from Thermotoga maritima: recognition and strand nicking mechanism. Biochemistry 40:8738–8748
Feng H, Dong L, Klutz AM, Aghaebrahim N, Cao W (2005) Defining amino acid residues involved in DNA–protein interactions and revelation of 3′-exonuclease activity in endonuclease V. Biochemistry 44:11486–11495
Huang J, Lu J, Barany F, Cao W (2002) Mutational analysis of endonuclease V from Thermotoga maritima. Biochemistry 41:8342–8350
Feng H, Dong L, Cao W (2006) Catalytic mechanism of endonuclease v: a catalytic and regulatory two-metal model. Biochemistry 45:10251–10259
Mi R, Alford-Zappala M, Kow YW, Cunningham RP, Cao W (2012) Human endonuclease V as a repair enzyme for DNA deamination. Mutat Res 735:12–18
Goedken ER, Marqusee S (2001) Co-crystal of Escherichia coli RNase HI with Mn2+ ions reveals two divalent metals bound in the active site. J Biol Chem 276:7266–7271
Hitchcock TM, Gao H, Cao W (2004) Cleavage of deoxyoxanosine-containing oligodeoxyribonucleotides by bacterial endonuclease V. Nucleic Acids Res 32:4071–4080
Horton NC, Perona JJ (2004) DNA cleavage by EcoRV endonuclease: two metal ions in three metal ion binding sites. Biochemistry 43:6841–6857
Kostrewa D, Winkler FK (1995) Mg2+ binding to the active site of EcoRV endonuclease: a crystallographic study of complexes with substrate and product DNA at 2 A resolution. Biochemistry 34:683–696
Vipond IB, Baldwin GS, Halford SE (1995) Divalent metal ions at the active sites of the EcoRV and EcoRI restriction endonucleases. Biochemistry 34:697–704
Nowotny M, Gaidamakov SA, Crouch RJ, Yang W (2005) Crystal structures of RNase H bound to an RNA/DNA hybrid: substrate specificity and metal-dependent catalysis. Cell 121:1005–1016
Pingoud V, Wende W, Friedhoff P, Reuter M, Alves J, Jeltsch A, Mones L, Fuxreiter M, Pingoud A (2009) On the divalent metal ion dependence of DNA cleavage by restriction endonucleases of the EcoRI family. J Mol Biol 393:140–160
Noble CG, Maxwell A (2002) The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two metal-ion mechanism. J Mol Biol 318:361–371
Zheng L, Li M, Shan J, Krishnamoorthi R, Shen B (2002) Distinct roles of two Mg2+ binding sites in regulation of murine flap endonuclease-1 activities. Biochemistry 41:10323–10331
Dupureur CM (2010) One is enough: insights into the two-metal ion nuclease mechanism from global analysis and computational studies. Metallomics: integrated biometal science 2:609–620
Yang W (2011) Nucleases: diversity of structure, function and mechanism. Q Rev Biophys 44:1–93
He B, Qing H, Kow YW (2000) Deoxyxanthosine in DNA is repaired by Escherichia coli endonuclease V. Mutat Res 459:109–114
Feng H, Klutz AM, Cao W (2005) Active site plasticity of endonuclease V from Salmonella typhimurium. Biochemistry 44:675–683
Guo G, Weiss B (1998) Endonuclease V (nfi) mutant of Escherichia coli K-12. J Bacteriol 180:46–51
Lin J, Gao H, Schallhorn KA, Harris RM, Cao W, Ke PC (2007) Lesion recognition and cleavage by endonuclease V: a single-molecule study. Biochemistry 46:7132–7137
Mi R, Abole AK, Cao W (2011) Dissecting endonuclease and exonuclease activities in endonuclease V from Thermotoga maritima. Nucleic Acids Res 39:536–544
Liu J, He B, Qing H, Kow YW (2000) A deoxyinosine specific endonuclease from hyperthermophile. Archaeoglobus fulgidus: a homolog of Escherichia coli endonuclease V. Mutat Res 461:169–177
Kanugula S, Pauly GT, Moschel RC, Pegg AE (2005) A bifunctional DNA repair protein from Ferroplasma acidarmanus exhibits O6-alkylguanine-DNA alkyltransferase and endonuclease V activities. Proc Natl Acad Sci USA 102:3617–3622
Emptage K, O’Neill R, Solovyova A, Connolly BA (2008) Interplay between DNA polymerase and proliferating cell nuclear antigen switches off base excision repair of uracil and hypoxanthine during replication in archaea. J Mol Biol 383:762–771
Moe A, Ringvoll J, Nordstrand LM, Eide L, Bjoras M, Seeberg E, Rognes T, Klungland A (2003) Incision at hypoxanthine residues in DNA by a mammalian homologue of the Escherichia coli antimutator enzyme endonuclease V. Nucleic Acids Res 31:3893–3900
Schouten KA, Weiss B (1999) Endonuclease V protects Escherichia coli against specific mutations caused by nitrous acid. Mutat Res 435:245–254
Weiss B (2001) Endonuclease V of Escherichia coli prevents mutations from nitrosative deamination during nitrate/nitrite respiration. Mutat Res 461:301–309
Burgis NE, Brucker JJ, Cunningham RP (2003) Repair system for noncanonical purines in Escherichia coli. J Bacteriol 185:3101–3110
Lopez-Olmos K, Hernandez MP, Contreras-Garduno JA, Robleto EA, Setlow P, Yasbin RE, Pedraza-Reyes M (2012) Roles of endonuclease V, uracil-DNA glycosylase, and mismatch repair in Bacillus subtilis DNA base-deamination-induced mutagenesis. J Bacteriol 194:243–252
Bradshaw JS, Kuzminov A (2003) RdgB acts to avoid chromosome fragmentation in Escherichia coli. Mol Microbiol 48:1711–1725
Lee CC, Yang YC, Goodman SD, Yu YH, Lin SB, Kao JT, Tsai KS, Fang WH (2010) Endonuclease V-mediated deoxyinosine excision repair in vitro. DNA Repair 9:1073–1079
Weiss B (2008) Removal of deoxyinosine from the Escherichia coli chromosome as studied by oligonucleotide transformation. DNA Repair 7:205–212
Bazar L, Collier G, Vanek P, Siles B, Kow Y, Doetsch P, Cunningham R, Chirikjian J (1999) Mutation identification DNA analysis system (MIDAS) for detection of known mutations. Electrophoresis 20:1141–1148
Huang J, Kirk B, Favis R, Soussi T, Paty P, Cao W, Barany F (2002) An endonuclease/ligase based mutation scanning method especially suited for analysis of neoplastic tissue. Oncogene 21:1909–1921
Pincas H, Pingle MR, Huang J, Lao K, Paty PB, Friedman AM, Barany F (2004) High sensitivity EndoV mutation scanning through real-time ligase proofreading. Nucleic Acids Res 32:e148
Gao H, Huang J, Barany F, Cao W (2007) Switching base preferences of mismatch cleavage in endonuclease V: an improved method for scanning point mutations. Nucleic Acids Res 35:e2
Turner DJ, Pingle MR, Barany F (2006) Harnessing asymmetrical substrate recognition by thermostable EndoV to achieve balanced linear amplification in multiplexed SNP typing. Biochem Cell Biol (Biochimie et biologie cellulaire) 84:232–242
Miyazaki K (2002) Random DNA fragmentation with endonuclease V: application to DNA shuffling. Nucleic Acids Res 30:e139
Stemmer WP (1994) DNA shuffling by random fragmentation and reassembly: in vitro recombination for molecular evolution. Proc Natl Acad Sci USA 91:10747–10751
Stemmer WP (1994) Rapid evolution of a protein in vitro by DNA shuffling. Nature 370:389–391
Wang Z, Wang HY, Feng H (2012) A simple and reproducible method for directed evolution: combination of random mutation with dITP and DNA fragmentation with endonuclease V. Mol Biotechnol. doi:10.1007/s12033-012-9516-9
Acknowledgments
This project was supported in part by CSREES/USDA (SC-1700274, technical contribution No. 6059), the Department of Defense (W81XWH-10-1-0385), and the National Institutes of Health (GM090141). I thank Drs. Bernard Weiss, Yoke Wah Kow, Richard Cunningham, Francis Barany, Brian Dominy and Rongjuan Mi for discussions.
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Cao, W. Endonuclease V: an unusual enzyme for repair of DNA deamination. Cell. Mol. Life Sci. 70, 3145–3156 (2013). https://doi.org/10.1007/s00018-012-1222-z
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DOI: https://doi.org/10.1007/s00018-012-1222-z