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Genome stability: recent insights in the topoisomerase reverse gyrase and thermophilic DNA alkyltransferase

  • Special Issue: Review
  • 10th International Congress on Extremophiles
  • Published:
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Abstract

Repair and defence of genome integrity from endogenous and environmental hazard is a primary need for all organisms. Natural selection has driven the evolution of multiple cell pathways to deal with different DNA damaging agents. Failure of such processes can hamper cell functions and induce inheritable mutations, which in humans may cause cancerogenicity or certain genetic syndromes, and ultimately cell death. A special case is that of hyperthermophilic bacteria and archaea, flourishing at temperatures higher than 80 °C, conditions that favor genome instability and thus call for specific, highly efficient or peculiar mechanisms to keep their genome intact and functional. Over the last few years, numerous studies have been performed on the activity, function, regulation, physical and functional interaction of enzymes and proteins from hyperthermophilic microorganisms that are able to bind, repair, bypass damaged DNA, or modify its structure or conformation. The present review is focused on two enzymes that act on DNA catalyzing unique reactions: reverse gyrase and DNA alkyltransferase. Although both enzymes belong to evolutionary highly conserved protein families present in organisms of the three domains (Eucarya, Bacteria and Archaea), recently characterized members from hyperthermophilic archaea show both common and peculiar features.

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References

  • Atomi H, Matsumi R, Imanaka T (2004) Reverse gyrase is not a prerequisite for hyperthermophilic life. J Bacteriol 186:4829–4833

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bizard A, Garnier F, Nadal M (2011) TopR2, the second reverse gyrase of Sulfolobus solfataricus, exhibits unusual properties. J Mol Biol 408:839–849

    Article  CAS  PubMed  Google Scholar 

  • Bouthier de la Tour C, Amrani L, Cossard R, Neuman KC, Serre MC, Duguet M (2008) Mutational analysis of the helicase-like domain of Thermotoga maritima reverse gyrase. J Biol Chem 283:27395–27402

    Article  CAS  PubMed  Google Scholar 

  • Brochier-Armanet C, Forterre P (2007) Widespread distribution of archaeal reverse gyrase in thermophilic bacteria suggests a complex history of vertical inheritance and lateral gene transfers. Archaea 2:83–93

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Brochier-Armanet C, Boussau B, Gribaldo S, Forterre P (2008) Mesophilic Crenarchaeota: proposal for a third archaeal phylum, the Thaumarchaeota. Nat Rev Microbiol 6:245–252

    Article  CAS  PubMed  Google Scholar 

  • Bussen W, Raynard S, Busygina V, Singh AK, Sung P (2007) Holliday junction processing activity of the BLM-Topo IIIα-BLAP75 complex. J Biol Chem 282:31484–31492

    Article  CAS  PubMed  Google Scholar 

  • Byrd AK, Raney KD (2012) Superfamily 2 helicases. Front Biosci 17:2070–2088

    Article  Google Scholar 

  • Campbell BJ, Smith JL, Hanson TE, Klotz MG, Stein LY, Lee CK, Wu D, Robinson JM, Khouri HM, Eisen JA, Cary SC (2009) Adaptations to submarine hydrothermal environments exemplified by the genome of Nautilia profundicola. PLoS Genet 5:e1000362

    Article  PubMed Central  PubMed  Google Scholar 

  • Capp C, Qian Y, Sage H, Huber H, Hsieh TS (2010) Separate and combined biochemical activities of the subunits of a naturally split reverse gyrase. J Biol Chem 285:39637–39645

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Champoux JJ (2001) DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 70:369–413

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Huang L (2006) Oligonucleotide cleavage and rejoining by topoisomerase III from the hyperthermophilic archaeon Sulfolobus solfataricus: temperature dependence and strand annealing-promoted DNA religation. Mol Microbiol 60:783–794

    Article  CAS  PubMed  Google Scholar 

  • Cubeddu L, White MF (2005) DNA damage detection by an archaeal single-stranded DNA-binding protein. J Mol Biol 353:507–516

    Article  CAS  PubMed  Google Scholar 

  • D’Amaro A, Rossi M, Ciaramella M (2007) Reverse gyrase: an unusual DNA manipulator of hyperthermophilic organisms. Ital J Biochem 56:103–109

    PubMed  Google Scholar 

  • Daniels DS, Mol CD, Arvai AS, Kanugula S, Pegg AE, Tainer JA (2000) Active and alkylated human AGT structures: a novel zinc site, inhibitor, and extrahelical base binding. EMBO J 19:1719–1730

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Daniels DS, Woo TT, Luu KX, Noll DM, Clarke ND, Pegg AE, Tainer JA (2004) DNA binding and nucleotide flipping by the human DNA repair protein AGT. Nat Struct Mol Biol 11:714–720

    Article  CAS  PubMed  Google Scholar 

  • De Felice M, Aria V, Esposito L, De Falco M, Pucci B, Rossi M, Pisani FM (2007) A novel DNA helicase with strand-annealing activity from the crenarchaeon Sulfolobus solfataricus. Biochem J 408:87–95

    Article  PubMed Central  PubMed  Google Scholar 

  • Déclais AC, Marsault J, Confalonieri F, de La Tour CB, Duguet M (2000) Reverse gyrase, the two domains intimately cooperate to promote positive supercoiling. J Biol Chem 275:19498–194504

    Article  PubMed  Google Scholar 

  • del Toro Duany Y, Klostermeier D (2011) Nucleotide-driven conformational changes in the reverse gyrase helicase-like domain couple the nucleotide cycle to DNA processing. Phys Chem Chem Phys 13:10009–10019

    Article  Google Scholar 

  • del Toro Duany Y, Jungblut SP, Schmidt AS, Klostermeier D (2008) The reverse gyrase helicase-like domain is a nucleotide-dependent switch that is attenuated by the topoisomerase domain. Nucleic Acids Res 36:5882–5895

    Article  Google Scholar 

  • del Toro Duany Y, Klostermeier D, Rudolph MG (2011) The conformational flexibility of the helicase-like domain from Thermotoga maritima reverse gyrase is restricted by the topoisomerase domain. Biochemistry 50:5816–5823

    Article  Google Scholar 

  • Duguid EM, Rice PA, He CJ (2005) The structure of the human AGT protein bound to DNA and its implications for damage detection. Mol Biol 350:657–666

    Article  CAS  Google Scholar 

  • Forterre P (2002) A hot story from comparative genomics: reverse gyrase is the only hyperthermophile-specific protein. Trends Genet 18:236–237

    Article  CAS  PubMed  Google Scholar 

  • Forterre P, Bergerat A, Lopez-Garcia P (1996) The unique DNA topology and DNA topoisomerases of hyperthermophilic archaea. FEMS Microbiol Rev 18:237–248

    Article  CAS  PubMed  Google Scholar 

  • Ganguly A, Del Toro Duany Y, Rudolph MG, Klostermeier D (2011) The latch modulates nucleotide and DNA binding to the helicase-like domain of Thermotoga maritima reverse gyrase and is required for positive DNA supercoiling. Nucleic Acids Res 39:1789–1800

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ganguly A, del Toro Duany Y, Klostermeier D (2013) Reverse gyrase transiently unwinds double-stranded DNA in an ATP-dependent reaction. J Mol Biol 425:32–40

    Article  CAS  PubMed  Google Scholar 

  • Guagliardi A, Napoli A, Rossi M, Ciaramella M (1997) Annealing of complementary DNA strands above the melting point of the duplex promoted by an archaeal protein. J Mol Biol 267:841–848

    Article  CAS  PubMed  Google Scholar 

  • Guipaud O, Marguet E, Noll KM, de la Tour CB, Forterre P (1997) Both DNA gyrase and reverse gyrase are present in the hyperthermophilic bacterium Thermotoga maritima. Proc Natl Acad Sci 94:10606–10611

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hashimoto H, Inoue T, Nishioka M, Fujiwara S, Takagi M, Imanaka T, Kai Y (1999) Hyperthermostable protein structure maintained by intra and inter-helix ion-pairs in archaeal O6-methylguanine-DNA methyltransferase. J Mol Biol 292:707–716

    Article  CAS  PubMed  Google Scholar 

  • Heine M, Chandra SB (2009) The linkage between reverse gyrase and hyperthermophiles: a review of their invariable association. J Microbiol 47:229–234

    Article  CAS  PubMed  Google Scholar 

  • Hsieh TS, Plank JL (2006) Reverse gyrase functions as a DNA renaturase: annealing of complementary single-stranded circles and positive supercoiling of a bubble substrate. J Biol Chem 281:5640–5647

    Article  CAS  PubMed  Google Scholar 

  • Hwang CS, Shemorry A, Varshavsky A (2009) Two proteolytic pathways regulate DNA repair by cotargeting the Mgt1 alkylguanine transferase. Proc Natl Acad Sci 106:2142–2147

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jamroze A, Perugino G, Valenti A, Naeem R, Rossi M, Muhammad A, Ciaramella M (2014) The reverse gyrase form Pyrobaculum calidifontis, a novel extremely thermophilic DNA topoisomerase endowed with DNA unwinding and annealing activities. J Biol Chem 289:3231–3243

    Article  CAS  PubMed  Google Scholar 

  • Jaxel C, Bouthier de la Tour M, Duguet M, Nadal (1996) Reverse gyrase gene from Sulfolobus shibatae B12: gene structure, transcription unit and comparative sequence analysis of the two domains. Nucleic Acids Res 24:4668–4675

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jaxel C, Duguet M, Nadal M (1999) Analysis of DNA cleavage by reverse gyrase from Sulfolobus shibatae B12. Eur J Biochem 260:103–111

    Article  CAS  PubMed  Google Scholar 

  • Kampmann M, Stock D (2004) Reverse gyrase has heat-protective DNA chaperone activity independent of supercoiling. Nucleic Acids Res 32:3537–3545

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kanugula S, Pegg EA (2003) Alkylation damage repair protein O6-alkylguanine-DNA-alkyltransferase from the hyperthermophiles Aquifex aeolicus and Archaeoglobus fulgidus. Biochem J 375:449–455

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kikuchi A, Asai K (1984) Reverse gyrase-a topoisomerase which introduces positive superhelical turns into DNA. Nature 309:677–681

    Article  CAS  PubMed  Google Scholar 

  • Larsen NB, Hickson ID (2013) RecQ helicases: conserved guardians of genomic integrity. Adv Exp Med Biol 767:161–184

    Article  CAS  PubMed  Google Scholar 

  • Leclere MM, Nishioka M, Yuasa T, Fujiwara S, Takagi M, Imanaka T (1998) The O6-methylguanine-DNA methyltransferase from the hyperthermophilic archaeon Pyrococcus sp. KOD1: a thermostable repair enzyme. Mol Gen Genet 258:69–77

    Article  CAS  PubMed  Google Scholar 

  • Li J, Liu J, Zhou J, Xiang H (2011) Functional evaluation of four putative DNA-binding regions in Thermoanaerobacter tengcongensis reverse gyrase. Extremophiles 15:281–291

    Article  CAS  PubMed  Google Scholar 

  • Lopez-Garcia P (1999) DNA supercoiling and temperature adaptation: a clue to early diversification of life? J Mol Evol 49:439–452

    Article  CAS  PubMed  Google Scholar 

  • Marguet E, Forterre P (1994) DNA stability at temperatures typical for hyperthermophiles. Nucleic Acids Res 22:1681–1686

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Miggiano R, Casazza V, Garavaglia S, Ciaramella M, Perugino G, Rizzi M, Rossi F (2013) Biochemical and structural studies of the mycobacterium tuberculosis O6-methylguanine methyltransferase and mutated variants. J Bacteriol 195:2728–2736

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mishina Y, Duguid EM, Chuan H (2006) Direct reversal of DNA alkylation damage. Chem Rev 106:215–232

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nadal M (2007) Reverse gyrase: an insight into the role of DNA-topoisomerases. Biochimie 89:447–455

    Article  CAS  PubMed  Google Scholar 

  • Napoli A, Zivanovic Y, Bocs C, Buhler C, Rossi M, Forterre P, Ciaramella M (2002) DNA bending, compaction and negative supercoiling by the architectural protein Sso7d of Sulfolobus solfataricus. Nucleic Acids Res 30:2656–2662

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Napoli A, Valenti A, Salerno V, Nadal M, Garnier F, Rossi M, Ciaramella M (2004) Reverse gyrase recruitment to DNA after UV light irradiation in Sulfolobus solfataricus. J Biol Chem 279:33192–33198

    Article  CAS  PubMed  Google Scholar 

  • Napoli A, Valenti A, Salerno V, Nadal M, Garnier F, Rossi M, Ciaramella M (2005) Functional interaction of reverse gyrase with single-strand binding protein of the archaeon Sulfolobus. Nucleic Acids Res 33:564–576

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nishikori S, Shiraki K, Okanojo M, Imanaka T, Takagi M (2004a) Equilibrium and kinetic stability of a hyperthermophilic protein, O6-methylguanine-DNA methyltransferase under various extreme conditions. J Biochem 136:503–508

    Article  CAS  PubMed  Google Scholar 

  • Nishikori S, Shiraki K, Yokota K, Izumikawa N, Fujiwara S, Hashimoto H, Imanaka T, Takagi M (2004b) Mutational effects on O(6)-methylguanine-DNA methyltransferase from hyperthermophile: contribution of ion-pair network to protein thermostability. J Biochem 135:525–532

    Article  CAS  PubMed  Google Scholar 

  • Nishikori S, Shiraki K, Fujiwara S, Imanaka T, Takagi M (2005) Unfolding mechanism of a hyperthermophilic protein O(6)-methylguanine-DNA methyltransferase. Biophys Chem 116:97–104

    Article  CAS  PubMed  Google Scholar 

  • Pegg AE (2011) Multifaceted roles of alkyltransferase and related proteins in DNA repair, DNA damage, resistance to chemotherapy, and research tools. Chem Res Toxicol 24:618–639

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Perugino G, Valenti A, D’amaro A, Rossi M, Ciaramella M (2009) Reverse gyrase and genome stability in hyperthermophilic organisms. Biochem Soc Trans 37:69–73

    Article  CAS  PubMed  Google Scholar 

  • Perugino G, Vettone A, Illiano G, Valenti A, Ferrara MC, Rossi M, Ciaramella M (2012) Activity and regulation of archaeal DNA alkyltransferase, conserved protein involved in repair of DNA alkylation damage. J Biol Chem 287:4222–4231

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Plank J, Hsieh TS (2009) Helicase-appended topoisomerases: new insight into the mechanism of directional strand transfer. J Biol Chem 284:30737–30741

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Plank JL, Wu J, Hsieh TS (2006) Topoisomerase IIIα and Bloom helicase can resolve a mobile double Holliday junction substrate through convergent branch migration. Proc Natl Acad Sci 103:11118–11123

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Qingming F, Kanugula S, Pegg AE (2005) Function of domains of human O6-alkylguanine-DNA-alkyltransferase. Biochemistry 44:15396–15405

    Article  Google Scholar 

  • Roberts A, Pelton JG, DE Wemmer (2006) Structural studies of MJ1529, an O6-methylguanine-DNA methyltransferase. Magn Reson Chem 44 Spec No:S71–S82

    Article  PubMed  Google Scholar 

  • Rodriguez AC (2002) Studies of a positive supercoiling machine. nucleotide hydrolysis and a multifunctional “latch” in the mechanism of reverse gyrase. J Biol Chem 277:29865–29873

    Article  CAS  PubMed  Google Scholar 

  • Rodríguez AC (2003) Investigating the role of the latch in the positive supercoiling mechanism of reverse gyrase. Biochemistry 42:5993–6004

    Article  PubMed  Google Scholar 

  • Rodríguez AC, Stock D (2002) Crystal structure of reverse gyrase: insights into the positive supercoiling of DNA. EMBO J 21:418–426

    Article  PubMed Central  PubMed  Google Scholar 

  • Romano V, Napoli A, Salerno V, Valenti A, Rossi M, Ciaramella M (2007) Lack of strand-specific repair of UV-induced DNA lesions in three genes of the archaeon Sulfolobus solfataricus. J Mol Biol 365:921–929

    Article  CAS  PubMed  Google Scholar 

  • Rudolph MG, del Toro Duany Y, Jungblut SP, Ganguly A, Klostermeier D (2013) Crystal structures of Thermotoga maritima reverse gyrase: inferences for the mechanism of positive DNA supercoiling. Nucleic Acids Res 41:1058–1070

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Salerno V, Napoli A, White MF, Rossi M, Ciaramella M (2003) Transcriptional response to DNA damage in the archaeon Sulfolobus solfataricus. Nucleic Acids Res 31:6127–6138

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shiraki K, Nishikori S, Fujiwara S, Hashimoto H, Kai Y, Takagi M, Imanaka T (2001) Comparative analyses of the conformational stability of a hyperthermophilic protein and its mesophilic counterpart. Eur J Biochem 268:4144–4150

    Article  CAS  PubMed  Google Scholar 

  • Skorvaga M, Raven ND, Margison GP (1998) Thermostable archaeal O6-alkylguanine-DNA alkyltransferases. Proc Natl Acad Sci 95:6711–6715

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tessmer I, Melikishvili M, Fried MG (2012) Cooperative cluster formation, DNA bending and base-flipping by O6-alkylguanine-DNA alkyltransferase. Nucleic Acids Res 40:8296–8308

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tubbs JL, Pegg AE, Tainer JA (2007) DNA binding, nucleotide flipping, and the helix-turn-helix motif in base repair by O6-alkylguanine-DNA-alkyltransferase and its implications for cancer chemotherapy. DNA Repair 6:1100–1115

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Valenti A, Napoli A, Ferrara MC, Nadal M, Rossi M, Ciaramella M (2006) Selective degradation of reverse gyrase and DNA fragmentation induced by alkylating agent in the archaeon Sulfolobus solfataricus. Nucleic Acids Res 34:2098–2108

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Valenti A, Perugino G, D’Amaro A, Cacace A, Napoli A, Rossi M, Ciaramella M (2008) Dissection of reverse gyrase activities: insight into the evolution of a thermostable molecular machine. Nucleic Acids Res 36:4587–4597

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Valenti A, Perugino G, Nohmi T, Rossi M, Ciaramella M (2009) Inhibition of translesion DNA polymerase by archaeal reverse gyrase. Nucleic Acids Res 37:4287–4295

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Valenti A, Perugino G, Varriale A, D’Auria S, Rossi M, Ciaramella M (2010) The archaeal topoisomerase reverse gyrase is a helix-destabilizing protein that unwinds four-way DNA junctions. J Biol Chem 285:36532–36541

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Valenti A, Perugino G, Rossi M, Ciaramella M (2011) Positive supercoiling in thermophiles and mesophiles: of the good and evil. Biochem Soc Trans 39:58–63

    Article  CAS  PubMed  Google Scholar 

  • Valenti A, De Felice M, Perugino G, Bizard A, Nadal M, Rossi M, Ciaramella M (2012) Synergic and opposing activities of thermophilic RecQ-like helicase and topoisomerase 3 proteins in Holliday junction processing and replication fork stabilization. J Biol Chem 287:30282–30295

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang JC (2002) Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 3:430–440

    Article  CAS  PubMed  Google Scholar 

  • Waters E, Hohn MJ, Ahel I, Graham DE, Adams MD, Barnstead M, Beeson KY, Bibbs L, Bolanos R, Keller M, Kretz K, Lin X, Mathur E, Ni J, Podar M, Richardson T, Sutton GG, Simon M, Soll D, Stetter KO, Short JM, Noordewier M (2003) The genome of Nanoarchaeum equitans: insights into early archaeal evolution and derived parasitism. Proc Natl Acad Sci 100:12984–12988

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Xu-Welliver M, Pegg AE (2002) Degradation of the alkylated form of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase. Carcinogenesis 23:823–830

    Article  CAS  PubMed  Google Scholar 

  • Yang CG, Garcia K, He C (2009) Damage detection and base flipping in direct DNA alkylation repair. ChemBioChem 10:417–423

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang C, Tian B, Li S, Ao X, Dalgaard K, Gökce S, Liang Y, She Q (2013) Genetic manipulation in Sulfolobus islandicus and functional analysis of DNA repair genes. Biochem Soc Trans 41:405–410

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Work in the authors’ laboratory is supported by FIRB-Futuro in Ricerca RBFR12OO1G_002 “Nematic”; Merit RBNE08YFN3; Ministero degli Affari Esteri (L.401/1990).

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  1. Institute of Biosciences and BioResources, Consiglio Nazionale delle Ricerche, Via P. Castellino 111, 80131, Naples, Italy

    Antonella Vettone, Giuseppe Perugino, Mosè Rossi, Anna Valenti & Maria Ciaramella

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  1. Antonella Vettone
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  2. Giuseppe Perugino
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  3. Mosè Rossi
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  4. Anna Valenti
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  5. Maria Ciaramella
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Correspondence to Maria Ciaramella.

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Communicated by H. Atomi.

This article is part of a special issue based on the 10th International Congress on Extremophiles held in Saint Petersburg, Russia, September 7–11, 2014.

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Vettone, A., Perugino, G., Rossi, M. et al. Genome stability: recent insights in the topoisomerase reverse gyrase and thermophilic DNA alkyltransferase. Extremophiles 18, 895–904 (2014). https://doi.org/10.1007/s00792-014-0662-9

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