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Ribonucleases pp 299-317 | Cite as

Structure and Function of RNase H Enzymes

  • Thomas Hollis
  • Nadine M. Shaban
Chapter
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC)

Abstract

RNase H enzymes are endonucleases that specifically cleave ribonucleotides within an RNA:DNA duplex. RNase H proteins are divided into type 1 and type 2 enzymes based on amino acid sequence similarities, substrate specificity, and structure. Both RNase H1 and RNase H2 enzymes play important roles in DNA replication, repair and transcription, and at least one type of RNase H is found in most organisms. Both RNase H1 and RNase H2 enzymes share a common structural fold of mixed β-sheets surrounded by several helices at their catalytic core. The enzymes utilize a two-metal-ion mechanism of phosphoryl hydrolysis mediated by divalent Mg2+ ions. RNase H1 enzymes are single polypeptide proteins with eukaryotic members containing an additional hybrid-binding domain (HBD). Eukaryotic RNase H2 is a heterotrimeric complex of the RNase H2A, RNase H2B, and RNase H2C proteins that are all necessary for enzymatic activity. Mutations in the human RNase H2 complex result in immune dysfunction.

Keywords

Proliferate Cell Nuclear Antigen Moloney Murine Leukemia Virus Okazaki Fragment Human RNase Bacterial RNase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Arudchandran A, Cerritelli S, Narimatsu S, Itaya M, Shin DY, Shimada Y, Crouch RJ (2000) The absence of ribonuclease H1 or H2 alters the sensitivity of Saccharomyces cerevisiae to hydroxyurea, caffeine and ethyl methanesulphonate: implications for roles of RNases H in DNA replication and repair. Genes Cells 5:789–802PubMedCrossRefGoogle Scholar
  2. Baaklini I, Hraiky C, Rallu F, Tse-Dinh YC, Drolet M (2004) RNase HI overproduction is required for efficient full-length RNA synthesis in the absence of topoisomerase I in Escherichia coli. Mol Microbiol 54:198–211PubMedCrossRefGoogle Scholar
  3. Baltimore D (1970) RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226:1209–1211PubMedCrossRefGoogle Scholar
  4. Bentin T, Cherny D, Larsen HJ, Nielsen PE (2005) Transcription arrest caused by long nascent RNA chains. Biochim Biophys Acta 1727:97–105PubMedCrossRefGoogle Scholar
  5. Cerritelli SM, Crouch RJ (1995) The non-RNase H domain of Saccharomyces cerevisiae RNase H1 binds double-stranded RNA: magnesium modulates the switch between double-stranded RNA binding and RNase H activity. RNA 1:246–259PubMedGoogle Scholar
  6. Cerritelli SM, Crouch RJ (1998) Cloning, expression, and mapping of ribonucleases H of human and mouse related to bacterial RNase HI. Genomics 53:300–307PubMedCrossRefGoogle Scholar
  7. Cerritelli SM, Fedoroff OY, Reid BR, Crouch RJ (1998) A common 40 amino acid motif in eukaryotic RNases H1 and caulimovirus ORF VI proteins binds to duplex RNAs. Nucleic Acids Res 26:1834–1840PubMedCrossRefGoogle Scholar
  8. Cerritelli SM, Frolova EG, Feng C, Grinberg A, Love PE, Crouch RJ (2003) Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice. Mol Cell 11:807–815PubMedCrossRefGoogle Scholar
  9. Chai Q, Qiu J, Chapados BR, Shen B (2001) Archaeoglobus fulgidus RNase HII in DNA replication: enzymological functions and activity regulation via metal cofactors. Biochem Biophys Res Commun 286:1073–1081PubMedCrossRefGoogle Scholar
  10. Champoux JJ, Schultz SJ (2009) Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription. FEBS J 276:1506–1516PubMedCrossRefGoogle Scholar
  11. Chapados BR, Chai Q, Hosfield DJ, Qiu J, Shen B, Tainer JA (2001) Structural biochemistry of a type 2 RNase H: RNA primer recognition and removal during DNA replication. J Mol Biol 307:541–556PubMedCrossRefGoogle Scholar
  12. Chon H, Matsumura H, Koga Y, Takano K, Kanaya S (2006) Crystal structure and structure-based mutational analyses of RNase HIII from Bacillus stearothermophilus: a new type 2 RNase H with TBP-like substrate-binding domain at the N terminus. J Mol Biol 356:165–178PubMedCrossRefGoogle Scholar
  13. Chon H, Vassilev A, Depamphilis ML, Zhao Y, Zhang J, Burgers PM, Crouch RJ, Cerritelli SM (2008) Contributions of the two accessory subunits, RNASEH2B and RNASEH2C, to the activity and properties of the human RNase H2 complex. Nucleic Acids Res 37:96–110PubMedCrossRefGoogle Scholar
  14. Crouch RJ, Arudchandran A, Cerritelli SM (2001) RNase H1 of Saccharomyces cerevisiae: methods and nomenclature. Methods Enzymol 341:395–413PubMedCrossRefGoogle Scholar
  15. Crow YJ, Rehwinkel J (2009) Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity. Hum Mol Genet 18:R130–R136PubMedCrossRefGoogle Scholar
  16. Crow YJ, Hayward BE, Parmar R, Robins P, Leitch A, Ali M, Black DN, van Bokhoven H, Brunner HG, Hamel BC, Corry PC, Cowan FM, Frints SG, Klepper J, Livingston JH, Lynch SA, Massey RF, Meritet JF, Michaud JL, Ponsot G, Voit T, Lebon P, Bonthron DT, Jackson AP, Barnes DE, Lindahl T (2006a) Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus. Nat Genet 38:917–920PubMedCrossRefGoogle Scholar
  17. Crow YJ, Leitch A, Hayward BE, Garner A, Parmar R, Griffith E, Ali M, Semple C, Aicardi J, Babul-Hirji R, Baumann C, Baxter P, Bertini E, Chandler KE, Chitayat D, Cau D, Dery C, Fazzi E, Goizet C, King MD, Klepper J, Lacombe D, Lanzi G, Lyall H, Martinez-Frias ML, Mathieu M, McKeown C, Monier A, Oade Y, Quarrell OW, Rittey CD, Rogers RC, Sanchis A, Stephenson JB, Tacke U, Till M, Tolmie JL, Tomlin P, Voit T, Weschke B, Woods CG, Lebon P, Bonthron DT, Ponting CP, Jackson AP (2006b) Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection. Nat Genet 38:910–916PubMedCrossRefGoogle Scholar
  18. De Vivo M, Dal Peraro M, Klein ML (2008) Phosphodiester cleavage in ribonuclease H occurs via an associative two-metal-aided catalytic mechanism. J Am Chem Soc 130:10955–10962PubMedCrossRefGoogle Scholar
  19. Delviks-Frankenberry KA, Nikolenko GN, Pathak VK (2010) The “connection” between HIV drug resistance and RNase H. Viruses 2:1476–1503PubMedCrossRefGoogle Scholar
  20. DeStefano JJ, Mallaber LM, Fay PJ, Bambara RA (1994) Quantitative analysis of RNA cleavage during RNA-directed DNA synthesis by human immunodeficiency and avian myeloblastosis virus reverse transcriptases. Nucleic Acids Res 22:3793–3800PubMedCrossRefGoogle Scholar
  21. Eder PS, Walder JA (1991) Ribonuclease H from K562 human erythroleukemia cells. Purification, characterization, and substrate specificity. J Biol Chem 266:6472–6479PubMedGoogle Scholar
  22. Eder PS, Walder RY, Walder JA (1993) Substrate specificity of human RNase H1 and its role in excision repair of ribose residues misincorporated in DNA. Biochimie 75:123–126PubMedCrossRefGoogle Scholar
  23. Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer EL, Eddy SR, Bateman A (2010) The Pfam protein families database. Nucleic Acids Res 38:D211–D222PubMedCrossRefGoogle Scholar
  24. Frank P, Albert S, Cazenave C, Toulme JJ (1994) Purification and characterization of human ribonuclease HII. Nucleic Acids Res 22:5247–5254PubMedCrossRefGoogle Scholar
  25. Frank P, Braunshofer-Reiter C, Wintersberger U (1998a) Yeast RNase H(35) is the counterpart of the mammalian RNase HI, and is evolutionarily related to prokaryotic RNase HII. FEBS Lett 421:23–26PubMedCrossRefGoogle Scholar
  26. Frank P, Braunshofer-Reiter C, Wintersberger U, Grimm R, Busen W (1998b) Cloning of the cDNA encoding the large subunit of human RNase HI, a homologue of the prokaryotic RNase HII. Proc Natl Acad Sci USA 95:12872–12877PubMedCrossRefGoogle Scholar
  27. Furfine ES, Reardon JE (1991) Reverse transcriptase. RNase H from the human immunodeficiency virus. Relationship of the DNA polymerase and RNA hydrolysis activities. J Biol Chem 266:406–412PubMedGoogle Scholar
  28. Gaidamakov SA, Gorshkova II, Schuck P, Steinbach PJ, Yamada H, Crouch RJ, Cerritelli SM (2005) Eukaryotic RNases H1 act processively by interactions through the duplex RNA-binding domain. Nucleic Acids Res 33:2166–2175PubMedCrossRefGoogle Scholar
  29. Gaiser F, Tan S, Richmond TJ (2000) Novel dimerization fold of RAP30/RAP74 in human TFIIF at 1.7 A resolution. J Mol Biol 302:1119–1127PubMedCrossRefGoogle Scholar
  30. 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 276:7266–7271PubMedCrossRefGoogle Scholar
  31. Gopalakrishnan V, Peliska JA, Benkovic SJ (1992) Human immunodeficiency virus type 1 reverse transcriptase: spatial and temporal relationship between the polymerase and RNase H activities. Proc Natl Acad Sci USA 89:10763–10767PubMedCrossRefGoogle Scholar
  32. Gotte M, Fackler S, Hermann T, Perola E, Cellai L, Gross HJ, Le Grice SF, Heumann H (1995) HIV-1 reverse transcriptase-associated RNase H cleaves RNA/RNA in arrested complexes: implications for the mechanism by which RNase H discriminates between RNA/RNA and RNA/DNA. EMBO J 14:833–841PubMedGoogle Scholar
  33. Haruki M, Tsunaka Y, Morikawa M, Iwai S, Kanaya S (2000) Catalysis by Escherichia coli ribonuclease HI is facilitated by a phosphate group of the substrate. Biochemistry 39:13939–13944PubMedCrossRefGoogle Scholar
  34. Haruki M, Tsunaka Y, Morikawa M, Kanaya S (2002) Cleavage of a DNA-RNA-DNA/DNA chimeric substrate containing a single ribonucleotide at the DNA-RNA junction with prokaryotic RNases HII. FEBS Lett 531:204–208PubMedCrossRefGoogle Scholar
  35. Hausen P, Stein H (1970) Ribonuclease H. An enzyme degrading the RNA moiety of DNA-RNA hybrids. Eur J Biochem 14:278–283PubMedCrossRefGoogle Scholar
  36. Hou J, Liu X, Pei D, Liu J (2007) RNase HII from Chlamydia pneumoniae discriminates mismatches incorporation into DNA-rN1-DNA/DNA duplexes. Biochem Biophys Res Commun 356:988–992PubMedCrossRefGoogle Scholar
  37. Huang L, Kim Y, Turchi JJ, Bambara RA (1994) Structure-specific cleavage of the RNA primer from Okazaki fragments by calf thymus RNase HI. J Biol Chem 269:25922–25927PubMedGoogle Scholar
  38. Itaya M (1990) Isolation and characterization of a second RNase H (RNase HII) of Escherichia coli K-12 encoded by the rnhB gene. Proc Natl Acad Sci USA 87:8587–8591PubMedCrossRefGoogle Scholar
  39. Itoh T, Tomizawa J (1979) Initiation of replication of plasmid ColE1 DNA by RNA polymerase, ribonuclease H, and DNA polymerase I. Cold Spring Harb Symp Quant Biol 43(Pt 1):409–417PubMedCrossRefGoogle Scholar
  40. Itoh T, Tomizawa J (1980) Formation of an RNA primer for initiation of replication of ColE1 DNA by ribonuclease H. Proc Natl Acad Sci USA 77:2450–2454PubMedCrossRefGoogle Scholar
  41. Itoh T, Tomizawa J (1982) Purification of ribonuclease H as a factor required for initiation of in vitro Co1E1 DNA replication. Nucleic Acids Res 10:5949–5965PubMedCrossRefGoogle Scholar
  42. Jeong HS, Backlund PS, Chen HC, Karavanov AA, Crouch RJ (2004) RNase H2 of Saccharomyces cerevisiae is a complex of three proteins. Nucleic Acids Res 32:407–414PubMedCrossRefGoogle Scholar
  43. Julias JG, McWilliams MJ, Sarafianos SG, Arnold E, Hughes SH (2002) Mutations in the RNase H domain of HIV-1 reverse transcriptase affect the initiation of DNA synthesis and the specificity of RNase H cleavage in vivo. Proc Natl Acad Sci USA 99:9515–9520PubMedCrossRefGoogle Scholar
  44. Kamada K, Roeder RG, Burley SK (2003) Molecular mechanism of recruitment of TFIIF-associating RNA polymerase C-terminal domain phosphatase (FCP1) by transcription factor IIF. Proc Natl Acad Sci USA 100:2296–2299PubMedCrossRefGoogle Scholar
  45. Kanaya S, Crouch RJ (1983) DNA sequence of the gene coding for Escherichia coli ribonuclease H. J Biol Chem 258:1276–1281PubMedGoogle Scholar
  46. Kanaya S, Crouch RJ (1984) The rnh gene is essential for growth of Escherichia coli. Proc Natl Acad Sci USA 81:3447–3451PubMedCrossRefGoogle Scholar
  47. Kanaya S, Katsuda-Nakai C, Ikehara M (1991) Importance of the positive charge cluster in Escherichia coli ribonuclease HI for the effective binding of the substrate. J Biol Chem 266:11621–11627PubMedGoogle Scholar
  48. Kao HI, Bambara RA (2003) The protein components and mechanism of eukaryotic Okazaki fragment maturation. Crit Rev Biochem Mol Biol 38:433–452PubMedCrossRefGoogle Scholar
  49. Katayanagi K, Miyagawa M, Matsushima M, Ishikawa M, Kanaya S, Ikehara M, Matsuzaki T, Morikawa K (1990) Three-dimensional structure of ribonuclease H from E. coli. Nature 347:306–309PubMedCrossRefGoogle Scholar
  50. Khaperskyy DA, Ammerman ML, Majovski RC, Ponticelli AS (2008) Functions of Saccharomyces cerevisiae TFIIF during transcription start site utilization. Mol Cell Biol 28:3757–3766PubMedCrossRefGoogle Scholar
  51. Kogoma T, Foster PL (1998) Physiological functions of E. coli RNase H. In: Crouch RJ, Toulmé JJ (eds) Ribonucleases H. John Libbey, Paris, pp 39–66Google Scholar
  52. Lai L, Yokota H, Hung LW, Kim R, Kim SH (2000) Crystal structure of archaeal RNase HII: a homologue of human major RNase H. Structure 8:897–904PubMedCrossRefGoogle Scholar
  53. Liang R, Liu X, Pei D, Liu J (2007) Biochemical characterization and functional complementation of ribonuclease HII and ribonuclease HIII from Chlamydophila pneumoniae AR39. Microbiology 153:787–793PubMedCrossRefGoogle Scholar
  54. Lim D, Orlova M, Goff SP (2002) Mutations of the RNase HC helix of the Moloney murine leukemia virus reverse transcriptase reveal defects in polypurine tract recognition. J Virol 76:8360–8373PubMedCrossRefGoogle Scholar
  55. Lim D, Gregorio GG, Bingman C, Martinez-Hackert E, Hendrickson WA, Goff SP (2006) Crystal structure of the moloney murine leukemia virus RNase H domain. J Virol 80:8379–8389PubMedCrossRefGoogle Scholar
  56. Lima WF, Nichols JG, Wu H, Prakash TP, Migawa MT, Wyrzykiewicz TK, Bhat B, Crooke ST (2004) Structural requirements at the catalytic site of the heteroduplex substrate for human RNase H1 catalysis. J Biol Chem 279:36317–36326PubMedCrossRefGoogle Scholar
  57. Lima WF, Rose JB, Nichols JG, Wu H, Migawa MT, Wyrzykiewicz TK, Siwkowski AM, Crooke ST (2007a) Human RNase H1 discriminates between subtle variations in the structure of the heteroduplex substrate. Mol Pharmacol 71:83–91PubMedCrossRefGoogle Scholar
  58. Lima WF, Rose JB, Nichols JG, Wu H, Migawa MT, Wyrzykiewicz TK, Vasquez G, Swayze EE, Crooke ST (2007b) The positional influence of the helical geometry of the heteroduplex substrate on human RNase H1 catalysis. Mol Pharmacol 71:73–82PubMedCrossRefGoogle Scholar
  59. Lin Y, Dent SY, Wilson JH, Wells RD, Napierala M (2010) R loops stimulate genetic instability of CTG.CAG repeats. Proc Natl Acad Sci USA 107:692–697PubMedCrossRefGoogle Scholar
  60. Mbisa JL, Nikolenko GN, Pathak VK (2005) Mutations in the RNase H primer grip domain of murine leukemia virus reverse transcriptase decrease efficiency and accuracy of plus-strand DNA transfer. J Virol 79:419–427PubMedCrossRefGoogle Scholar
  61. McWilliams MJ, Julias JG, Sarafianos SG, Alvord WG, Arnold E, Hughes SH (2006) Combining mutations in HIV-1 reverse transcriptase with mutations in the HIV-1 polypurine tract affects RNase H cleavages involved in PPT utilization. Virology 348:378–388PubMedCrossRefGoogle Scholar
  62. Molling K, Bolognesi DP, Bauer H, Busen W, Plassmann HW, Hausen P (1971) Association of viral reverse transcriptase with an enzyme degrading the RNA moiety of RNA-DNA hybrids. Nat New Biol 234:240–243PubMedCrossRefGoogle Scholar
  63. Murante RS, Henricksen LA, Bambara RA (1998) Junction ribonuclease: an activity in Okazaki fragment processing. Proc Natl Acad Sci USA 95:2244–2249PubMedCrossRefGoogle Scholar
  64. Muroya A, Tsuchiya D, Ishikawa M, Haruki M, Morikawa M, Kanaya S, Morikawa K (2001) Catalytic center of an archaeal type 2 ribonuclease H as revealed by X-ray crystallographic and mutational analyses. Protein Sci 10:707–714PubMedCrossRefGoogle Scholar
  65. Nick McElhinny SA, Kumar D, Clark AB, Watt DL, Watts BE, Lundstrom EB, Johansson E, Chabes A, Kunkel TA (2010a) Genome instability due to ribonucleotide incorporation into DNA. Nat Chem Biol 6:774–781PubMedCrossRefGoogle Scholar
  66. Nick McElhinny SA, Watts BE, Kumar D, Watt DL, Lundstrom EB, Burgers PM, Johansson E, Chabes A, Kunkel TA (2010b) Abundant ribonucleotide incorporation into DNA by yeast replicative polymerases. Proc Natl Acad Sci USA 107:4949–4954PubMedCrossRefGoogle Scholar
  67. Nowotny M, Yang W (2006) Stepwise analyses of metal ions in RNase H catalysis from substrate destabilization to product release. EMBO J 25:1924–1933PubMedCrossRefGoogle Scholar
  68. 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 121:1005–1016PubMedCrossRefGoogle Scholar
  69. Nowotny M, Gaidamakov SA, Ghirlando R, Cerritelli SM, Crouch RJ, Yang W (2007) Structure of human RNase H1 complexed with an RNA/DNA hybrid: insight into HIV reverse transcription. Mol Cell 28:264–276PubMedCrossRefGoogle Scholar
  70. Nowotny M, Cerritelli SM, Ghirlando R, Gaidamakov SA, Crouch RJ, Yang W (2008) Specific recognition of RNA/DNA hybrid and enhancement of human RNase H1 activity by HBD. EMBO J 27:1172–1181PubMedCrossRefGoogle Scholar
  71. Ohtani N, Haruki M, Morikawa M, Crouch RJ, Itaya M, Kanaya S (1999a) Identification of the genes encoding Mn2+−dependent RNase HII and Mg2+−dependent RNase HIII from Bacillus subtilis: classification of RNases H into three families. Biochemistry 38:605–618PubMedCrossRefGoogle Scholar
  72. Ohtani N, Haruki M, Morikawa M, Kanaya S (1999b) Molecular diversities of RNases H. J Biosci Bioeng 88:12–19PubMedCrossRefGoogle Scholar
  73. Perrino FW, Harvey S, Shaban NM, Hollis T (2009) RNaseH2 mutants that cause Aicardi-Goutieres syndrome are active nucleases. J Mol Med 87:25–30PubMedCrossRefGoogle Scholar
  74. Pileur F, Toulme JJ, Cazenave C (2000) Eukaryotic ribonucleases HI and HII generate characteristic hydrolytic patterns on DNA-RNA hybrids: further evidence that mitochondrial RNase H is an RNase HII. Nucleic Acids Res 28:3674–3683PubMedCrossRefGoogle Scholar
  75. Qiu J, Qian Y, Frank P, Wintersberger U, Shen B (1999) Saccharomyces cerevisiae RNase H(35) functions in RNA primer removal during lagging-strand DNA synthesis, most efficiently in cooperation with Rad27 nuclease. Mol Cell Biol 19:8361–8371PubMedGoogle Scholar
  76. Ramantani G, Kohlhase J, Hertzberg C, Innes AM, Engel K, Hunger S, Borozdin W, Mah JK, Ungerath K, Walkenhorst H, Richardt HH, Buckard J, Bevot A, Siegel C, von Stulpnagel C, Ikonomidou C, Thomas K, Proud V, Niemann F, Wieczorek D, Hausler M, Niggemann P, Baltaci V, Conrad K, Lebon P, Lee-Kirsch MA (2010) Expanding the phenotypic spectrum of lupus erythematosus in aicardi-goutieres syndrome. Arthritis Rheum 62(5):1469–1477PubMedCrossRefGoogle Scholar
  77. Repaske R, Hartley JW, Kavlick MF, O’Neill RR, Austin JB (1989) Inhibition of RNase H activity and viral replication by single mutations in the 3′ region of Moloney murine leukemia virus reverse transcriptase. J Virol 63:1460–1464PubMedGoogle Scholar
  78. Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, Artuch R, Montalto SA, Bacino CA, Barroso B, Baxter P, Benko WS, Bergmann C, Bertini E, Biancheri R, Blair EM, Blau N, Bonthron DT, Briggs T, Brueton LA, Brunner HG, Burke CJ, Carr IM, Carvalho DR, Chandler KE, Christen HJ, Corry PC, Cowan FM, Cox H, D’Arrigo S, Dean J, De Laet C, De Praeter C, Dery C, Ferrie CD, Flintoff K, Frints SG, Garcia-Cazorla A, Gener B, Goizet C, Goutieres F, Green AJ, Guet A, Hamel BC, Hayward BE, Heiberg A, Hennekam RC, Husson M, Jackson AP, Jayatunga R, Jiang YH, Kant SG, Kao A, King MD, Kingston HM, Klepper J, van der Knaap MS, Kornberg AJ, Kotzot D, Kratzer W, Lacombe D, Lagae L, Landrieu PG, Lanzi G, Leitch A, Lim MJ, Livingston JH, Lourenco CM, Lyall EG, Lynch SA, Lyons MJ, Marom D, McClure JP, McWilliam R, Melancon SB, Mewasingh LD, Moutard ML, Nischal KK, Ostergaard JR, Prendiville J, Rasmussen M, Rogers RC, Roland D, Rosser EM, Rostasy K, Roubertie A, Sanchis A, Schiffmann R, Scholl-Burgi S, Seal S, Shalev SA, Corcoles CS, Sinha GP, Soler D, Spiegel R, Stephenson JB, Tacke U, Tan TY, Till M, Tolmie JL, Tomlin P, Vagnarelli F, Valente EM, Van Coster RN, Van der Aa N, Vanderver A, Vles JS, Voit T, Wassmer E, Weschke B, Whiteford ML, Willemsen MA, Zankl A, Zuberi SM, Orcesi S, Fazzi E, Lebon P, Crow YJ (2007) Clinical and molecular phenotype of Aicardi-Goutieres syndrome. Am J Hum Genet 81:713–725PubMedCrossRefGoogle Scholar
  79. Robert F, Coulombe B (2001) Use of site-specific protein-DNA photocrosslinking to analyze the molecular organization of the RNA polymerase II initiation complex. Methods Mol Biol 148:383–393PubMedGoogle Scholar
  80. Robert F, Douziech M, Forget D, Egly JM, Greenblatt J, Burton ZF, Coulombe B (1998) Wrapping of promoter DNA around the RNA polymerase II initiation complex induced by TFIIF. Mol Cell 2:341–351PubMedCrossRefGoogle Scholar
  81. Rossi ML, Purohit V, Brandt PD, Bambara RA (2006) Lagging strand replication proteins in genome stability and DNA repair. Chem Rev 106:453–473PubMedCrossRefGoogle Scholar
  82. Rychlik MP, Chon H, Cerritelli SM, Klimek P, Crouch RJ, Nowotny M (2010) Crystal structures of RNase H2 in complex with nucleic acid reveal the mechanism of RNA-DNA junction recognition and cleavage. Mol Cell 40:658–670PubMedCrossRefGoogle Scholar
  83. Rydberg B, Game J (2002) Excision of misincorporated ribonucleotides in DNA by RNase H (type 2) and FEN-1 in cell-free extracts. Proc Natl Acad Sci USA 99:16654–16659PubMedCrossRefGoogle Scholar
  84. Sarafianos SG, Das K, Tantillo C, Clark AD Jr, Ding J, Whitcomb JM, Boyer PL, Hughes SH, Arnold E (2001) Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA. EMBO J 20:1449–1461PubMedCrossRefGoogle Scholar
  85. Schatz O, Mous J, Le Grice SF (1990) HIV-1 RT-associated ribonuclease H displays both endonuclease and 3′–5′ exonuclease activity. EMBO J 9:1171–1176PubMedGoogle Scholar
  86. Schultz SJ, Champoux JJ (2008) RNase H activity: structure, specificity, and function in reverse transcription. Virus Res 134:86–103PubMedCrossRefGoogle Scholar
  87. Shaban NM, Harvey S, Perrino FW, Hollis T (2010) The structure of the mammalian RNase H2 complex provides insight into RNA.NA hybrid processing to prevent immune dysfunction. J Biol Chem 285:3617–3624PubMedCrossRefGoogle Scholar
  88. Shultz RW, Tatineni VM, Hanley-Bowdoin L, Thompson WF (2007) Genome-wide analysis of the core DNA replication machinery in the higher plants Arabidopsis and rice. Plant Physiol 144:1697–1714PubMedCrossRefGoogle Scholar
  89. Stein H, Hausen P (1969) Enzyme from calf thymus degrading the RNA moiety of DNA-RNA Hybrids: effect on DNA-dependent RNA polymerase. Science 166:393–395PubMedCrossRefGoogle Scholar
  90. Tadokoro T, Kanaya S (2009) Ribonuclease H: molecular diversities, substrate binding domains, and catalytic mechanism of the prokaryotic enzymes. FEBS J 276:1482–1493PubMedCrossRefGoogle Scholar
  91. Telesnitsky A, Goff SP (1997) Reverse transcriptase and the generation of retroviral DNA. In: Coffin JM, Hughes SH, Varmus HE (eds) Retroviruses. Cold Spring Harbor Laboratory Press, Cold Spring HarborGoogle Scholar
  92. Temin HM, Mizutani S (1970) RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226:1211–1213PubMedCrossRefGoogle Scholar
  93. Tisdale M, Schulze T, Larder BA, Moelling K (1991) Mutations within the RNase H domain of human immunodeficiency virus type 1 reverse transcriptase abolish virus infectivity. J Gen Virol 72(Pt 1):59–66PubMedCrossRefGoogle Scholar
  94. Tramontano E, Di Santo R (2010) HIV-1 RT-associated RNase H function inhibitors: recent advances in drug development. Curr Med Chem 17:2837–2853PubMedCrossRefGoogle Scholar
  95. Usongo V, Nolent F, Sanscartier P, Tanguay C, Broccoli S, Baaklini I, Drlica K, Drolet M (2008) Depletion of RNase HI activity in Escherichia coli lacking DNA topoisomerase I leads to defects in DNA supercoiling and segregation. Mol Microbiol 69:968–981PubMedGoogle Scholar
  96. Yang W, Hendrickson WA, Crouch RJ, Satow Y (1990) Structure of ribonuclease H phased at 2 A resolution by MAD analysis of the selenomethionyl protein. Science 249:1398–1405PubMedCrossRefGoogle Scholar
  97. Yang W, Lee JY, Nowotny M (2006) Making and breaking nucleic acids: two-Mg2+−ion catalysis and substrate specificity. Mol Cell 22:5–13PubMedCrossRefGoogle Scholar
  98. Yu F, Liu X, Zhan P, De Clercq E (2008) Recent advances in the research of HIV-1 RNase H inhibitors. Mini Rev Med Chem 8:1243–1251PubMedCrossRefGoogle Scholar
  99. Zhang WH, Svarovskaia ES, Barr R, Pathak VK (2002) Y586F mutation in murine leukemia virus reverse transcriptase decreases fidelity of DNA synthesis in regions associated with adenine-thymine tracts. Proc Natl Acad Sci USA 99:10090–10095PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of BiochemistryCenter for Structural Biology, Wake Forest School of MedicineWinston-SalemUSA

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