Advertisement

Role of DNA repair in the protection against genotoxic stress

  • Ulrike Camenisch
  • Hanspeter Naegeli
Part of the Experientia Supplementum book series (EXS, volume 99)

Abstract

The genome of all organisms is constantly attacked by a variety of environmental and endogenous mutagens that cause cell death, apoptosis, senescence, genetic diseases and cancer. To mitigate these deleterious endpoints of genotoxic reactions, living organisms have evolved one or more mechanisms for repairing every type of naturally occurring DNA lesion. For example, double-strand breaks are rapidly religated by non-homologous end-joining. Homologous recombination is used for the high-fidelity repair of interstrand cross-links, double-strand breaks and other DNA injuries that disrupt the replication fork. Some genotoxic lesions inflicted by alkylating agents can be repaired by direct reversal of DNA damage. The base excision repair pathway takes advantage of multiple DNA glycosylases to remove modified or incorrect bases. Finally, the nucleotide excision repair machinery provides a versatile strategy to monitor DNA quality and eliminate all forms of helix-distorting DNA lesions, including a wide diversity of carcinogen adducts. The efficiency of DNA repair responses is enhanced by their coupling to transcription and coordination with the cell cycle circuit.

Keywords

Nucleotide Excision Repair Base Excision Repair Xeroderma Pigmentosum Genotoxic Stress Cockayne Syndrome 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Lindahl T (1993) Instability and decay of the primary structure of DNA. Nature 362: 709–715PubMedGoogle Scholar
  2. 2.
    Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T (2006) DNA Repair and Mutagenesis. ASM Press, Washington D.C.Google Scholar
  3. 3.
    Hanawalt PC (2007) Paradigms for the three Rs: DNA replication, recombination, and repair. Mol Cell 28: 702–707PubMedGoogle Scholar
  4. 4.
    Lopes M, Foiani M, Sogo JM (2006) Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Mol Cell 21: 15–27PubMedGoogle Scholar
  5. 5.
    Naegeli H (1994) Roadblocks and detours during DNA replication: Mechanisms of mutagenesis in mammalian cells. BioEssays 16: 557–564PubMedGoogle Scholar
  6. 6.
    van Gent DC, Hoeijmakers JH, Kanaar R (2001) Chromosomal stability and the DNA doublestranded break connection. Nat Rev Genet 2: 196–206PubMedGoogle Scholar
  7. 7.
    Povirk LF (1996) DNA damage and mutagenesis by radiomimetic DNA-cleaving agents: Bleomycin, neocarzinostatin and other enediynes. Mutat Res 355: 71–89PubMedGoogle Scholar
  8. 8.
    Li X, Heyer W-D (2008) Homologous recombination in DNA repair and DNA damage tolerance. Cell Res 18: 99–113PubMedGoogle Scholar
  9. 9.
    Cox MM (2002) The nonmutagenic repair of broken replication forks via recombination. Mutat Res 510: 107–120PubMedGoogle Scholar
  10. 10.
    Weterings E, Chen DJ (2008) The endless tale of non-homologous end-joining. Cell Res 18: 114–124PubMedGoogle Scholar
  11. 11.
    Dip R, Naegeli H (2005) More than just strand breaks: The recognition of structural DNA discontinuities by DNA-dependent protein kinase catalytic subunit. FASEB J 19: 704–715PubMedGoogle Scholar
  12. 12.
    Lieber MR, Ma Y, Pannicke U, Schwarz K (2003) Mechanisms and regulation of human nonhomologous DNA end-joining. Nat Rev Mol Cell Biol 4: 712–720PubMedGoogle Scholar
  13. 13.
    Buck D, Malivert L, de Chasseval R, Barraud A, Fondanèche MC, Sanal O, Plebani A, Stéphan JL, Hufnagel M, le Deist F et al (2006) Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell 124: 287–299PubMedGoogle Scholar
  14. 14.
    Ahnesorg P, Smith P, Jackson SP (2006) XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 124: 301–313PubMedGoogle Scholar
  15. 15.
    Downs JA, Jackson SP (2004) A means to a DNA end: The many roles of Ku. Nat Rev Mol Cell Biol 5: 367–378PubMedGoogle Scholar
  16. 16.
    Smith GC, Jackson SP (1999) The DNA-dependent protein kinase. Genes Dev 13: 916–934PubMedGoogle Scholar
  17. 17.
    Reddy YV, Ding Q, Lees-Miller SP, Meek K, Ramsden DA (2004) Non-homologous end joining requires that the DNA-PK complex undergo an autophosphorylation-dependent rearrangement at DNA ends. J Biol Chem 279: 39408–39413PubMedGoogle Scholar
  18. 18.
    DeFazio LG, Stansel RM, Griffith JD, Chu G (2002) Synapsis of DNA ends by DNA-dependent protein kinase. EMBO J 21: 3192–3200PubMedGoogle Scholar
  19. 19.
    Weterings E, Verkaik NS, Bruggenwirth HT, Hoeijmakers JH, van Gent DC (2003) The role of DNA-dependent protein kinase in synapsis of DNA ends. Nucleic Acids Res 31: 7238–7246PubMedGoogle Scholar
  20. 20.
    Ma Y, Pannicke U, Schwarz K, Lieber MR (2002) Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination. Cell 108: 781–794PubMedGoogle Scholar
  21. 21.
    Mahajan KN, McElhinny SA, Mitchell BS, Ramsden DA (2002) Association of DNA polymerase ? (pol ?) with Ku and ligase IV: Role of pol ? in end-joining double-strand break repair. Mol Cell Biol 22: 5194–5202PubMedGoogle Scholar
  22. 22.
    van Heemst D, Brugmans L, Verkaik NS, van Gent DC (2004) End-joining of blunt DNA doublestrand breaks in mammalian fibroblasts is precise and requires DNA-PK and XRCC4. DNA Rep 3: 43–50Google Scholar
  23. 23.
    Tsai CJ, Kim SA, Chu G (2007) Cernunnos/XLF promotes the ligation of mismatched and noncohesive DNA ends. Proc Natl Acad Sci USA 104: 7851–7856PubMedGoogle Scholar
  24. 24.
    Tischfield JA (1997) Loss of heterozygosity or: How I learned to stop worrying and love mitotic recombination. Am J Hum Genet 61: 995–999PubMedGoogle Scholar
  25. 25.
    Helleday T (2003) Pathways for mitotic homologous recombination. Mutat Res 532: 103–115PubMedGoogle Scholar
  26. 26.
    Trujillo KM,Yuan SS, Lee EY, Sung P (1998) Nuclease activities in a complex of human recombination and DNA repair factors Rad50, Mre11, and p95. J Biol Chem 273: 21447–21450PubMedGoogle Scholar
  27. 27.
    Sung P (1994) Catalysis of ATP-dependent homologous DNA pairing and strand exchange by yeast RAD51 protein. Science 265: 1241–1243PubMedGoogle Scholar
  28. 28.
    Ogawa T, Yu X, Shinohara A, Egelman EH (1993) Similarity of the yeast RAD51 filament to the bacterial RecA filament. Science 259: 1896–1899PubMedGoogle Scholar
  29. 29.
    Conway AB, Lynch TW, Zhang Y, Fortin GS, Fung CW, Symington LS, Rice PA (2004) Crystal structure of a Rad51 filament. Nat Struct Mol Biol 11: 791–796PubMedGoogle Scholar
  30. 30.
    Constantinou A, Chen XB, McGowan CH, West SC (2002) Holliday junction resolution in human cells: Two junction endonucleases with distinct substrate specificities. EMBO J 21: 5577–5585PubMedGoogle Scholar
  31. 31.
    Niedernhofer LJ, Daniels JS, Rouzer CA, Greene RE, Marnett LJ (2003) Malodialdehyde, a product of lipid peroxidation, is utagenic in human cells. J Biol Chem 278: 31426–31433PubMedGoogle Scholar
  32. 32.
    Hanada K, Budzowska M, Modesti M, Maas A, Wyman C, Essers J, Kanaar R (2006) The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strand breaks. EMBO J 25: 4921–4932PubMedGoogle Scholar
  33. 33.
    Kennedy RD, D’Andrea AD (2005) The Fanconi Anemia/BRCA pathway: New faces in the crowd. Genes Dev 19: 2925–2940PubMedGoogle Scholar
  34. 34.
    Sancar A (1996) DNA excision repair. Annu Rev Biochem 65: 43–81PubMedGoogle Scholar
  35. 35.
    Wood RD (1997) Nucleotide excision repair in mammalian cells. J Biol Chem 272: 23465–23468PubMedGoogle Scholar
  36. 36.
    Loechler EL, Green CL, Essigmann J (1984) In vivo mutagenesis by O6-methylguanine built into a unique site in a viral genome. Proc Natl Acad Sci USA 81: 6271–6275PubMedGoogle Scholar
  37. 37.
    Preston BD, Singer B, Loeb LA (1986) Mutagenic potential of O4-methylthymine in vivo determined by an enzymatic approach to site-specific mutagenesis. Proc Natl Acad Sci USA 83: 8501–8505PubMedGoogle Scholar
  38. 38.
    Mitra S, Kaina B (1993) Regulation of repair of alkylation damage in mammalian genomes. Prog Nucleic Acids Res Mol Biol 44: 109–142Google Scholar
  39. 39.
    Pegg AE, Byers TL (1992) Repair of DNA containing O6-alkylguanine. FASEB J 6: 2302–2310PubMedGoogle Scholar
  40. 40.
    Samson L, Han S, Marquis JC, Rasmussen LJ (1997) Mammalian DNA repair methyltransferases shield O4MeT from nucleotide excision repair. Carcinogenesis 18: 919–924PubMedGoogle Scholar
  41. 41.
    Moore MH, Gulbis JM, Dodson EJ, Demple B, Moody PC (1994) Crystal structure of a suicidal DNA repair protein: The Ada O6-methylguanine-DNA methyltransferase from E. coli. EMBO J 13: 1495–1501PubMedGoogle Scholar
  42. 42.
    Tsuzuki T, Sakumi K, Shiraishi A (1996) Targeted disruption of the DNA repair methyltransferase gene renders mice hypersensitive to alkylating agents. Carcinogenesis 17: 1215–1220PubMedGoogle Scholar
  43. 43.
    Iwakuma T, Sakumi K, Nakatsuru Y, Kawate H, Igarashi H, Shiraishi A, Tsuzuki T, Ishikawa T, Sekiguchi M (1997) High incidence of nitrosamine-induced tumorigenesis in mice lacking DNA repair methyltransferase. Carcinogenesis 18: 1631–1635PubMedGoogle Scholar
  44. 44.
    Glassner BJ, Weeda G, Allan JM, Broekhof JL, Carla NH, Donker I, Engelward BP, Hampson RJ, Hersmus R, Hickman MJ et al (1999) DNA repair methyltransferase (Mgmt) knockout mice are sensitive to the lethal effects of chemotherapeutic alkylating agents. Mutagenesis 14: 339–347PubMedGoogle Scholar
  45. 45.
    Dumenco LL, Allay E, Norton K, Gerson SL (1993) The prevention of thymic lymphomas in transgenic mice by human O6-akylguanine DNA alkyltransferase. Science 259: 219–222PubMedGoogle Scholar
  46. 46.
    Nakatsuru Y, Matsukuma S, Nemoto N, Sugano H, Sekiguchi M, Ishikawa T (1993) O6-methylguanine-DNA methyltransferase protects against nitrosamine-induced hepatocarcinogenesis. Proc Natl Acad Sci USA 90: 6468–6472PubMedGoogle Scholar
  47. 47.
    Becker K, Dosch J, Gregel CM, Martin BA, Kaina B (1996) Targeted expression of human O(6)-methylguanine-DNA methyltransferase (MGMT) in transgenic mice protects against tumor initiation in two-stage skin carcinogenesis. Cancer Res 56: 3244–3249PubMedGoogle Scholar
  48. 48.
    Liu L, Qin X, Gerson SL (1999) Reduced lung tumorigenesis in human methylguanine DNAmethyltransferase transgenic mice achieved by expression of transgene within the target cell. Carcinogenesis 20: 279–284PubMedGoogle Scholar
  49. 49.
    Sklar RM, Strauss BS (1981) Removal of O6-methylguanine from DNA of normal and Xeroderma pigmentosum-derived lymphoblastoid lines. Nature 289: 417–420PubMedGoogle Scholar
  50. 50.
    Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343: 1350–1354PubMedGoogle Scholar
  51. 51.
    Gerson SL (2002) Clinical relevance of MGMT in the treatment of cancer. J Clin Oncol 20: 2388–2399PubMedGoogle Scholar
  52. 52.
    Trewick SC, Henshaw TF, Hausinger RP, Lindahl T, Sedgwick B (2002) Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature 419: 174–178PubMedGoogle Scholar
  53. 53.
    Tsujikawa K, Koike K, Kitae K, Shinkawa A, Arima H, Suzuki T, Tsuchiya M, Makino Y, Furukawa T, Konishi N, Yamamoto H (2007) Expression and sub-cellular localization of human ABH family molecules. J Cell Mol Med 11: 1105–1116PubMedGoogle Scholar
  54. 54.
    Aas PA, Otterlei M, Falnes PO, Vagbo CB, Skorpen F, Akbari M, Sundheim O, Bjoras M, Slupphaug G, Seeberg E, Krokan HE (2003) Human and bacterial oxidative demethylase repair alkylation damage in both RNA and DNA. Nature 421: 859–863PubMedGoogle Scholar
  55. 55.
    Duncan T, Trewick SC, Koivisto P, Bates PA, Lindahl T, Sedgwick B (2002) Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci USA 99: 16660–16665PubMedGoogle Scholar
  56. 56.
    Ringvoll J, Nordstrand LM, Vagbo CB, Talstad V, Reite K, Aas PA, Lauritzen KH, Liabakk NB, Bjork A, Doughty RW et al (2006) Repair deficient mice reveal mABH2 as the primary oxidative demethylase for repairing 1meA and 3meC lesions in DNA. EMBO J 25: 2189–2198PubMedGoogle Scholar
  57. 57.
    Mitchell D (2006) Revisiting the photochemistry of solar UVA in human skin. Proc Natl Acad Sci USA 103: 13567–13568PubMedGoogle Scholar
  58. 58.
    Kelner A (1949) Effect of visible light on the recovery of Streptomyces griseus conidia from ultraviolet irradiation injury. Proc Natl Acad Sci USA 35: 73–79Google Scholar
  59. 59.
    Dulbecco R (1949) Reactivation of ultraviolet-inactivated bacteriophage with visible light. Nature 163: 949–950Google Scholar
  60. 60.
    Rupert CS, Goodgal SH, Herriott RM (1958) Photoreactivation in vitro of ultraviolet-inactivated Hemophilus influenzae transforming factor. J Gen Physiol 41: 451–471PubMedGoogle Scholar
  61. 61.
    Park HW, Kim ST, Sancar A, Deisenhofer J (1995) Crystal structure of DNA photolyase from Escherichia coli. Science 268: 1866–1872Google Scholar
  62. 62.
    Essen LO, Klar T (2006) Light-driven DNA repair by photolyases. Cell Mol Life Sci 63: 1266–1277PubMedGoogle Scholar
  63. 63.
    Kato T, Todo T, Ayaki H, Ishizaki K, Morita T, Mitra S, Ikenaga M (1994) Cloning of a marsupial DNA photolyase gene and the lack of related nucleotide sequences in placental mammals. Nucleic Acids Res 22: 4119–4124PubMedGoogle Scholar
  64. 64.
    Li YF, Kim ST, Sancar A (1993) Evidence for lack of photoreactivating enzyme in humans. Proc Natl Acad Sci USA 90: 4389–4393PubMedGoogle Scholar
  65. 65.
    Naegeli H (1997) Mechanisms of DNA Damage Recognition in Mammalian Cells. Springer, New YorkGoogle Scholar
  66. 66.
    Demple B, Harrison L (1994) Repair of oxidative damage to DNA: Enzymology and biology. Annu Rev Biochem 63: 915–948PubMedGoogle Scholar
  67. 67.
    Dodson ML, Michaels ML, Lloyd RS (1994) Unified catalytic mechanism for DNA glycosylases. J Biol Chem 269: 32709–32712PubMedGoogle Scholar
  68. 68.
    Slupphaug G, Mol CD, Kavli B, Arvai AS, Krokan HE, Tainer JA (1996) A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA. Nature 386: 87–92Google Scholar
  69. 69.
    Saparbaev M, Kleibl K, Laval J (1995) Escherichia coli, Saccharomyces cerevisiae, rat, and human 3-methyladenine DNA glycosylase repair 1,N6-ethenoadenine when present in DNA. Nucleic Acids Res 23: 3750–3755PubMedGoogle Scholar
  70. 70.
    Engelward BP, Weeda G, Wyatt MD, Broekhof JL, de Wit J, Donker I, Allan JM, Gold B, Hoeijmakers JH, Samson LD (1997) Base excision repair deficient mice lacking the Aag alkyladenine DNA glycosylase. Proc Natl Acad Sci USA 94: 13087–13092PubMedGoogle Scholar
  71. 71.
    Hang B, Singer B, Margison GP, Elder RH (1997) Targeted deletion of alkylpurine-DNA-N-glycosylase in mice eliminates repair of 1,N6-ethenoadenine and hypoxanthine but not of 3,N4-ethenocytosine or 8-oxoguanine. Proc Natl Acad Sci USA 94: 12869–12874PubMedGoogle Scholar
  72. 72.
    Thayer MM, Ahern H, Xing D, Cunningham RP, Tainer JA (1995) Novel DNA binding motifs in the DNA repair enzyme endonuclease III crystal structure. EMBO J 14: 4108–4120PubMedGoogle Scholar
  73. 73.
    Nash HM, Bruner SD, Schärer OD, Kawate T, Addona TA, Spooner E, Lane WS, Verdine GL (1996) Cloning of a yeast 8-oxoguanine DNA glycosylase reveals the existence of a base-excision DNA-repair protein superfamily. Curr Biol 6: 968–980PubMedGoogle Scholar
  74. 74.
    Labahn J, Schärer OD, Long A, Ezaz-Nikpay K, Verdine GL, Ellenberger TE (1996) Structural basis for the excision repair of alkylation-damaged DNA. Cell 86: 321–329PubMedGoogle Scholar
  75. 75.
    Parikh SS, Mol CD, Slupphaug G, Bharati S, Krokan HE, Tainer JA (1998) Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA. EMBO J 17: 5214–5226PubMedGoogle Scholar
  76. 76.
    Lau AY, Schärer OD, Samson L, Verdine GL, Ellenberger T (1998) Crystal structure of a human alkylbase-DNA repair enzyme complexed to DNA: Mechanisms for nucleotide flipping and base excision. Cell 95: 249–258PubMedGoogle Scholar
  77. 77.
    Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: Mechanisms, mutation, and disease. FASEB J 17: 1195–1214PubMedGoogle Scholar
  78. 78.
    Aruoma OI, Halliwell B, Dizdaroglu M (1989) Iron ion-dependent modification of bases in DNA by the superoxide radical-generating system hypoxanthine/xanthine oxidase. J Biol Chem 264: 13024–13028PubMedGoogle Scholar
  79. 79.
    Gajewski E, Rao G, Nackerdien Z, Dizdaroglu M (1990) Modification of DNA bases in mammalian chromatin by radiation-generated free radicals. Biochemistry 29: 7876–7882PubMedGoogle Scholar
  80. 80.
    Sung JS, Demple B (2006) Roles of base excision repair subpathways in correcting oxidized abasic sites in DNA. FEBS J 273: 1620–1629PubMedGoogle Scholar
  81. 81.
    van der Kemp PA, Thomas D, Barbey R, de Oliveira R, Boiteux S (1996) Cloning and expression in Escherichia coli of the OGG1 gene of Saccharomyces cerevisiae, which codes for a DNA glycosylase that excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine. Proc Natl Acad Sci USA 93: 5197–5202PubMedGoogle Scholar
  82. 82.
    Hsu GW, Ober M, Carell T, Beese LS (2004) Error-prone replication of oxidatively damaged DNA by a high-fidelity DNA polymerase. Nature 431: 217–221PubMedGoogle Scholar
  83. 83.
    Bjoras M, Seeberg E, Luna L, Pearl LH, Barrett TE (2002) Reciprocal “flipping” underlies substrate recognition and catalytic activation by the human 8-oxo-guanine DNA glycosylase. J Mol Biol 317: 171–177PubMedGoogle Scholar
  84. 84.
    Bruner SD, Norman DPG, Verdine GL (2000) Structural basis for recognition and repair of the endogenous mutagen 8-oxoguanine in DNA. Nature 403: 859–866PubMedGoogle Scholar
  85. 85.
    Stivers JT, Jiang YL (2003) A mechanistic perspective on the chemistry of DNA repair glycosylases. Chem Rev 103: 2729–2759PubMedGoogle Scholar
  86. 86.
    Shinmura K, Kohno T, Kasai H, Koda K, Sugimura H, Yokota J (1998) Infrequent mutations of the hOGG1 gene, that is involved in the excision of 8-hydroxyguanine in damaged DNA, in human gastric cancer. Jpn J Cancer Res 89: 825–828PubMedGoogle Scholar
  87. 87.
    Audebert M, Radicella JP, Dizdaroglu M (2000) Effect of single mutations in the OGG1 gene found in human tumors on the substrate specificity of the Ogg1 protein. Nucleic Acids Res 28: 2672–2678PubMedGoogle Scholar
  88. 88.
    Kuznetsov NA, Koval VV, Nevinsky GA, Douglas KT, Zharkov DO, Fedorova OS (2007) Kinetic 146 U. Camenisch and H. Naegeli conformational analysis of human 8-oxoguanine-DNA glycosylase. J Biol Chem 282: 1029–1038PubMedGoogle Scholar
  89. 89.
    Chen L, Haushalter KA, Lieber CM, Verdine GL (2002) Direct visualization of a DNA glycosylase searching for damage. Chem Biol 9: 345–350PubMedGoogle Scholar
  90. 90.
    Banerjee A, Yang W, Karplus M, Verdine GL (2005) Structure of a repair enzyme interrogating undamaged DNA elucidates recognition of damaged DNA. Nature 434: 612–618PubMedGoogle Scholar
  91. 91.
    Sidorenko VS, Nevinsky GA, Zharkov DO (2007) Mechanism of interaction between human 8-oxoguanine-DNA glycosylase and AP endonuclease. DNA Rep 6: 317–328Google Scholar
  92. 92.
    Wilson DM, Bohr VA (2007) The mechanics of base excision repair, and its relationship to aging and disease. DNA Rep 6: 544–559Google Scholar
  93. 93.
    Klungland A, Rosewell I, Hollenbach S, Larsen E, Daly G, Epe B, Seeberg E, Lindahl T, Barnes DE (1999) Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage. Proc Natl Acad Sci USA 96: 13300–13305PubMedGoogle Scholar
  94. 94.
    Sakumi K, Tominaga Y, Furuichi M, Xu P, Tsuzuki T, Sekiguchi M, Nakabeppu Y (2003) Ogg1 knockout-associated lung tumorigenesis and its suppression by Mth1 gene disruption. Cancer Res 63: 902–905PubMedGoogle Scholar
  95. 95.
    Chevillard S, Radicella JP, Levalois C, Lebeau J, Poupon MF, Oudard S, Dutrillaux B, Boiteux S (1998) Mutations in OGG1, a gene involved in the repair of oxidative DNA damage, are found in human lung and kidney tumours. Oncogene 16: 3083–3086PubMedGoogle Scholar
  96. 96.
    Dou H, Mitra S, Hazra TK (2003) Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. J Biol Chem 278: 49679–49684PubMedGoogle Scholar
  97. 97.
    Hu J, de Souza-Pinto C, Haraguchi K, Hogue BA, Jaruga P, Greenberg MM, Dizdaroglu M, Bohr VA (2005) Repair of formamidopyrimidines in DNA involves different glycosylases: Role of the OGG1, NTH1, and NEIL1 enzymes. J Biol Chem 280: 40544–40551PubMedGoogle Scholar
  98. 98.
    Hazra TK, Das A, Das S, Choudhury S, Kow YW, Roy R (2006) Oxidative DNA damage repair in mammalian cells: A new perspective. DNA Rep 6: 470–480Google Scholar
  99. 99.
    Lovell MA, Markesbery WR (2001) Ratio of 8-hydroxyguanine in intact DNA to free 8-hydroxyguanine is increased in Alzheimer disease ventricular cerebrospinal fluid. Arch Neurol 58: 392–396PubMedGoogle Scholar
  100. 100.
    Wang J, Xiong S, Xie C, Markesbery WR, Lovell MA (2005) Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer’s disease. J Neurochem 93: 953–962PubMedGoogle Scholar
  101. 101.
    Mao G, Pan X, Zhu BB, Zhang Y, Yuan F, Huang J, Lovell MA, Lee MP, Markesbery WR, Li GM, Gu L (2007) Identification and characterization of OGG1 mutations in patients with Alzheimer’s disease. Nucleic Acids Res 35: 2759–2766PubMedGoogle Scholar
  102. 102.
    de Laat WL, Jaspers NG, Hoeijmakers JH (1999) Molecular mechanism of nucleotide excision repair. Genes Dev 13: 768–785PubMedGoogle Scholar
  103. 103.
    Satoh MS, Jones CJ, Wood RD, Lindahl T (1993) DNA excision-repair defect of Xeroderma pigmentosum prevents removal of a class of oxygen free radical-induced base lesions. Proc Natl Acad Sci USA 90: 6335–6339PubMedGoogle Scholar
  104. 104.
    Reardon JT, Bessho T, Kung HC, Bolton PH, Sancar A (1997) In vitro repair of oxidative DNA damage by human nucleotide excision repair system: Possible explanation for neurodegeneration in Xeroderma pigmentosum patients. Proc Natl Acad Sci USA 94: 9463–9468PubMedGoogle Scholar
  105. 105.
    Kuraoka I, Bender C, Romieu A, Cadet J, Wood RD, Lindahl T (2000) Removal of oxygen freeradical-induced 5’,8-purine cyclodeoxynucleosides from DNA by the nucleotide excision-repair pathway in human cells. Proc Natl Acad Sci USA 97: 3832–3837PubMedGoogle Scholar
  106. 106.
    Reardon JT, Sancar A (2006) Repair of DNA-polypeptide crosslinks by human excision nuclease. Proc Natl Acad Sci USA 103: 4056–4061PubMedGoogle Scholar
  107. 107.
    Maillard O, Solyom S, Naegeli H (2007) An aromatic sensor with aversion to damaged strands confers versatility to DNA repair. PLoS Biol 5: e79PubMedGoogle Scholar
  108. 108.
    Kraemer KH, Lee MM, Scotto J (1984) DNA repair protects against cutaneous and internal neoplasia: Evidence from Xeroderma pigmentosum. Carcinogenesis 5: 511–514PubMedGoogle Scholar
  109. 109.
    D’Errico M, Parlanti E, Teson M, de Jesus BM, Degan P, Calcagnile A, Jaruga P, Bjoras M, Crescenzi M, Pedrini AM et al (2006) New functions of XPC in the protection of human skin cells from oxidative damage. EMBO J 25: 4305–4315PubMedGoogle Scholar
  110. 110.
    Nakane H, Takeuchi S, Yuba S, Saijo M, Nakatsu Y, Murai H, Nakatsuru Y, Ishikawa T, Hirota S, Kitamura Ye et al (1995) High incidence of ultraviolet-B-or chemical-carcinogen-induced skin tumors in mice lacking the Xeroderma pigmentosumgroup A gene. Nature 377: 165–168PubMedGoogle Scholar
  111. 111.
    de Vries A, van Oostrom CT, Hofhuis FM, Dortant PM, Berg RJ, de Gruijl FR, Wester PW, van Kreijl CF, Capel PJ, van Steeg H, Verbeck SJ (1995) Increased susceptibility to ultraviolet-B and carcinogens of mice lacking the DNA excision repair gene XPA. Nature 377: 169–173PubMedGoogle Scholar
  112. 112.
    de Vries A, van Oostrom CT, Dortant PM, Beems RB, van Kreijl CF, Capel PJ, van Steeg H (1997) Spontaneous liver tumors and benzopyrene-induced lymphomas in XPA-deficient mice. Mol Carcinog 19: 46–53PubMedGoogle Scholar
  113. 113.
    Sands AT, Abuin A, Sanchez A, Conti CJ, Bradley A (1995) High susceptibility to ultravioletinduced carcinogenesis in mice lacking XPC. Nature 377: 162–165PubMedGoogle Scholar
  114. 114.
    Cheo DL, Burns DK, Meira LB, Houle JF, Friedberg EC (1999) Mutational inactivation of the Xeroderma pigmentosum group C gene confers predisposition to 2-acetylaminofluorene-induced liver and lung cancer and to spontaneous testicular cancer in Trp53-/-mice. Cancer Res 59: 771–775PubMedGoogle Scholar
  115. 115.
    Aboussekhra A, Biggerstaff M, Shivji MK, Vilpo JA, Moncollin V, Podust VN, Protic M, Hubscher U, Egly JM, Wood RD (1995) Mammalian DNA nucleotide excision repair reconstituted with purified protein components. Cell 80: 859–868PubMedGoogle Scholar
  116. 116.
    Mu D, Park CH, Matsunaga T, Hsu DS, Reardon JT, Sancar A (1995) Reconstitution of human DNA repair excision nuclease in a highly defined system. J Biol Chem 270: 2415–2418PubMedGoogle Scholar
  117. 117.
    Araujo SJ, Tirode F, Coin F, Pospiech H, Syvaoja JE, Stucki M, Hubscher U, Egly JM, Wood RD (2000) Nucleotide excision repair of DNA with recombinant human proteins: Definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK. Genes Dev 14: 349–359PubMedGoogle Scholar
  118. 118.
    Volker M, Moné MJ, Karmakar P, van Hoffen A, Schul W, Vermeulen W, Hoeijmakers JH, van Driel R, van Zeeland AA, Mullenders LH (2001) Sequential assembly of the nucleotide excision repair factors in vivo. Mol Cell 8: 213–224PubMedGoogle Scholar
  119. 119.
    Nishi R, Okuda Y, Watanabe E, Mori T, Iwai S, Masutani C, Sugasawa K, Hanaoka F (2005) Centrin 2 stimulates nucleotide excision repair by interacting with Xeroderma pigmentosum group C protein. Mol Cell Biol 25: 5664–5674PubMedGoogle Scholar
  120. 120.
    Mu D, Wakasugi M, Hsu DS, Sancar A (1997) Characterization of reaction intermediates of human excision repair nuclease. J Biol Chem 272: 28971–28979PubMedGoogle Scholar
  121. 121.
    Evans E, Moggs JG, Hwang JR, Egly JM, Wood RD (1997) Mechanism of open complex and dual incision formation by human nucleotide excision repair factors. EMBO J 16: 6559–6573PubMedGoogle Scholar
  122. 122.
    Coin F, Marinoni JC, Rodolfo C, Fribourg S, Pedrini AM, Egly JM (1998) Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH. Nat Genet 20: 184–188PubMedGoogle Scholar
  123. 123.
    O’Donovan A, Davies AA, Moggs JG, West SC, Wood RD (1994) XPG endonuclease makes the 3’ incision in human DNA nucleotide excision repair. Nature 371: 432–435PubMedGoogle Scholar
  124. 124.
    Huang JC, Svoboda DL, Reardon JT, Sancar A (1992) Human nucleotide excision nuclease removes thymine dimers from DNA by incising the 22nd phosphodiester bond 5’ and the 6th phosphodiester bond 3’ to the photodimer. Proc Natl Acad Sci USA 89: 3664–3668PubMedGoogle Scholar
  125. 125.
    Missura M, Buterin T, Hindges R, Hubscher U, Kasparkova J, Brabec V, Naegeli H (2001) Double-check probing of DNA bending and unwinding by XPA-RPA: An architectural function in DNA repair. EMBO J 20: 3554–3564PubMedGoogle Scholar
  126. 126.
    Hess MT, Schwitter U, Petretta M, Giese B, Naegeli H (1997) Bipartite substrate discrimination by human nucleotide excision repair. Proc Natl Acad Sci USA 94: 6664–6669PubMedGoogle Scholar
  127. 127.
    Buschta-Hedayat N, Buterin T, Hess MT, Missura M, Naegeli H (1999) Recognition of nonhybridizing base pairs during nucleotide excision repair of DNA. Proc Natl Acad Sci USA 96: 6090–6095PubMedGoogle Scholar
  128. 128.
    Buterin T, Hess MT, Luneva N, Geacintov NE, Amin S, Kroth H, Seidel A, Naegeli H (2000) Unrepaired fjord region polycyclic aromatic hydrocarbon-DNA adducts in ras codon 61 mutational hot spots. Cancer Res 60: 1849–1856PubMedGoogle Scholar
  129. 129.
    Hess MT, Gunz D, Luneva N, Geacintov NE, Naegeli H (1997) Base pair conformation-dependent excision of benzo[a]pyrene diol epoxide-guanine adducts by human nucleotide excision repair enzymes. Mol Cell Biol 17: 7069–7076PubMedGoogle Scholar
  130. 130.
    Choi CH, Kalosakas G, Rasmussen KO, Hiromura M, Bishop AR, Usheva A (2004) DNA dynamically directs its own transcription initiation. Nucleic Acids Res 32: 1584–1590PubMedGoogle Scholar
  131. 131.
    Blagoev KB, Alexandrov BS, Goodwin EH, Bishop AR (2006) Ultra-violet light induced changes in DNA dynamics may enhance TT-dimer recognition. DNA Rep 5: 863–867Google Scholar
  132. 132.
    Cosman M, Hingerty BE, Luneva N, Amin S, Geacintov NE, Broyde S, Patel DJ (1996) Solution conformation of the (-)-cis-anti-benzo[a]pyrenyl-dG adduct opposite dC in a DNA duplex: Intercalation of the covalently attached BP ring into the helix with base displacement of the mod148 U. Camenisch and H. Naegeli ified deoxyguanosine into the major groove. Biochemistry 35: 9850–9863PubMedGoogle Scholar
  133. 133.
    Bertrand-Burggraf E, Kemper B, Fuchs RP (1994) Endonuclease VII of phage T4 nicks N-2-acetylaminofluorene-induced DNA structures in vitro. Mutat Res 314: 287–295PubMedGoogle Scholar
  134. 134.
    Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ et al (1994) Purification and cloning of a nucleotide excision repair complex involving the Xeroderma pigmentosum group C protein and a human homologue of yeast RAD23. EMBO J 13: 1831–1843PubMedGoogle Scholar
  135. 135.
    Sugasawa K, Ng JM, Masutani C, Iwai S, van der Spek PJ, Eker AP, Hanaoka F, Bootsma D, Hoeijmakers JH (1998) Xeroderma pigmentosumgroup C protein complex is the initiator of global genome nucleotide excision repair. Mol Cell 2: 223–232PubMedGoogle Scholar
  136. 136.
    Batty D, Rapic-Otrin V, Levine AS, Wood RD (2000) Stable binding of human XPC complex to irradiated DNA confers strong discrimination for damaged sites. J Mol Biol 300: 275–290PubMedGoogle Scholar
  137. 137.
    Kusumoto R, Masutani C, Sugasawa K, Iwai S, Araki M, Uchida A, Mizukoshi T, Hanaoka F (2001) Diversity of the damage recognition step in the global genomic nucleotide excision repair in vitro. Mutat Res 485: 219–227Google Scholar
  138. 138.
    Janicijevic A, Sugasawa K, Shimizu Y, Hanaoka F, Wijgers N, Djurica M, Hoeijmakers JH, Wyman C (2003) DNA bending by the human damage recognition complex XPC-HR23B. DNA Rep 2: 325–336Google Scholar
  139. 139.
    Anantharaman V, Koonin EV, Aravind L (2001) Peptide-N-glycanases and DNA repair proteins, Xp-C/Rad4, are, respectively, active and inactivated enzymes sharing a common transglutaminase fold. Hum Mol Genet 10: 1627–1630PubMedGoogle Scholar
  140. 140.
    Min JH, Pavletich NP (2007) Recognition of DNA damage by the Rad4 nucleotide excision repair protein. Nature 449: 570–575PubMedGoogle Scholar
  141. 141.
    Buterin T, Meyer C, Giese B, Naegeli H (2005) DNA quality control by conformational readout on the undamaged strand of the double helix. Chem Biol 12: 913–922PubMedGoogle Scholar
  142. 142.
    Reardon JT, Sancar A (2003) Recognition and repair of the cyclobutane thymine dimer, a major cause of skin cancers, by the human excision nuclease. Genes Dev 17: 2539–2551PubMedGoogle Scholar
  143. 143.
    Feldberg RS, Grossman L (1976) A DNA binding protein from human placenta specific for ultraviolet damaged DNA. Biochemistry 15: 2402–2408PubMedGoogle Scholar
  144. 144.
    Tang JY, Hwang BJ, Ford JM, Hanawalt PC, Chu G (2000) Xeroderma pigmentosum p48 gene enhances global genomic repair and suppresses UV-induced mutagenesis. Mol Cell 5: 737–744PubMedGoogle Scholar
  145. 145.
    Rapic-Otrin V, Navazza V, Nardo T, Botta E, McLenigan M, Bisi DC, Levine AS, Stefanini M (2003) True XP group E patients have a defective UV-damaged DNA binding protein complex and mutations in DDB2 which reveal the functional domains of its p48 product. Hum Mol Genet 12: 1507–1522PubMedGoogle Scholar
  146. 146.
    Fujiwara Y, Masutani C, Mizukoshi T, Kondo J, Hanaoka F, Iwai S (1999) Characterization of DNA recognition by the human UV-damaged DNA-binding protein. J Biol Chem 274: 20027–20033PubMedGoogle Scholar
  147. 147.
    Kulaksiz G, Reardon JT, Sancar A (2005) Xeroderma pigmentosumcomplementation group E protein (XPE/DDB2): Purification of various complexes of XPE and analyses of their damaged DNA binding and putative DNA repair properties. Mol Cell Biol 25: 9784–9792PubMedGoogle Scholar
  148. 148.
    Payne A, Chu G (1994) Xeroderma pigmentosumgroup E binding factor recognizes a broad spectrum of DNA damage. Mutat Res 310: 89–102PubMedGoogle Scholar
  149. 149.
    Shiyanov P, Nag A, Raychaudhuri P (1999) Cullin 4A associates with the UV-damaged DNAbinding protein DDB. J Biol Chem 274: 35309–35312PubMedGoogle Scholar
  150. 150.
    Nag A, Bondar T, Shiv S, Raychaudhuri P (2001) The Xeroderma pigmentosum group E gene product DDB2 is a specific target of cullin 4A in mammalian cells. Mol Cell Biol 21: 6738–6747PubMedGoogle Scholar
  151. 151.
    Sugasawa K, Okuda Y, Saijo M, Nishi R, Matsuda N, Chu G, Mori T, Iwai S, Tanaka K, Hanaoka F (2005) UV-induced ubiquitylation of XC protein mediated by UV-DDB-ubiquitin ligase complex. Cell 121: 387–400PubMedGoogle Scholar
  152. 152.
    Rapic-Otrin V, McLenigan MP, Bisi DC, Gonzalez M, Levine AS (2002) Sequential binding of UV DNA damage binding factor and degradation of the p48 subunit as early events after UV irradiation. Nucleic Acids Res 30: 2588–2598PubMedGoogle Scholar
  153. 153.
    Schultz P, Fribourg S, Poterszman A, Mallouh V, Moras D, Egly JM (2000) Molecular structure of human TFIIH. Cell 102: 599–607PubMedGoogle Scholar
  154. 154.
    Zurita M, Merino C (2003) The transcriptional complexity of the TFIIH complex. Trends Genet 19: 578–584PubMedGoogle Scholar
  155. 155.
    Yokoi M, Masutani C, Maekawa T, Sugasawa K, Ohkuma Y, Hanaoka F (2000) The Xeroderma Role of DNA repair in the protection against genotoxic stress 149 pigmentosumgroup C protein complex XPC-HR23B plays an important role in the recruitment of transcription factor IIH to damaged DNA. J Biol Chem 275: 9870–9875PubMedGoogle Scholar
  156. 156.
    Guzder SN, Qiu H, Sommers CH, Sung P, Prakash L, Prakash S (1994) DNA repair gene RAD3 of S. cerevisiae is essential for transcription by RNA polymerase II. Nature 367: 91–94PubMedGoogle Scholar
  157. 157.
    Dillingham MS, Spies M, Kowalczykowski SC (2003) RecBCD enzyme is a bipolar DNA helicase. Nature 423: 893–897PubMedGoogle Scholar
  158. 158.
    Naegeli H, Bardwell L, Friedberg EC (1992) The DNA helicase and adenosine triphosphatase activities of yeast Rad3 protein are inhibited by DNA damage. J Biol Chem 267: 392–398PubMedGoogle Scholar
  159. 159.
    Naegeli H, Bardwell L, Friedberg EC (1993) Inhibition of Rad3 DNA helicase activity by DNA adducts and abasic sites: Implications for the role of a DNA helicase in damage-specific incision of DNA. Biochemistry 32: 613–621PubMedGoogle Scholar
  160. 160.
    Rudolf J, Makrantoni V, Ingledew WJ, Stark MJ, White MF (2006) The DNA repair helicases XPD and FancJ have essential iron-sulfur domains. Mol Cell 23: 801–808PubMedGoogle Scholar
  161. 161.
    Pugh RA, Honda M, Leesley H, Thomas A, Lin Y, Nilges MJ, Cann IK, Spies M (2008) The ironcontaining domain is essential in Rad3 helicases for coupling of ATP hydrolysis to DNA translocation and for targeting the helicase to the single-stranded DNA-double-stranded DNA junction. J Biol Chem 283: 1732–1743PubMedGoogle Scholar
  162. 162.
    Mitchell JR, Hoeijmakers JH, Niedernhofer LJ (2003) Divide and conquer: Nucleotide excision repair battles cancer and ageing. Curr Opin Cell Biol 15: 232–240PubMedGoogle Scholar
  163. 163.
    Kalogeraki VS, Tornaletti S, Hanawalt PC (2003) Transcription arrest at a lesion in the transcribed DNA strand in vitro is not affected by a nearby lesion in the opposite strand. J Biol Chem 278: 19558–19564PubMedGoogle Scholar
  164. 164.
    Hanawalt PC (1994) Transcription-coupled repair and human disease. Science 266: 1957–1958PubMedGoogle Scholar
  165. 165.
    Bohr VA, Smith CA, Okumoto DS, Hanawalt PC (1985) DNA repair in an active gene: Removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall. Cell 40: 359–369PubMedGoogle Scholar
  166. 166.
    Mellon I, Spivak G, Hanawalt PC (1987) Selective removal of transcription-blocking DNA damage from the transcribed strand of the mammalian DHFR gene. Cell 51: 241–249PubMedGoogle Scholar
  167. 167.
    Dimitri A, Goodenough AK, Guengerich FP, Broyde S, Scicchitano DA (2008) Transcription processing at 1,N2-ethenoguanine by human RNA polymerase II and bacteriophage T7 RNA polymerase. J Mol Biol 375: 353–366PubMedGoogle Scholar
  168. 168.
    Schinecker TM, Perlow RA, Broyde S, Geacintov NE, Scicchitano DA (2003) Human RNA polymerase II is partially blocked by DNA adducts derived from tumorigenic benzo[c]phenanthrene diol epoxides: Relating biological consequences to conformational preferences. Nucleic Acids Res 31: 6004–6015PubMedGoogle Scholar
  169. 169.
    Tornaletti S, Patrick SM, Turchi JJ, Hanawalt PC (2003) Behavior of T7 RNA polymerase and mammalian RNA polymerase II at site-specific cisplatin adducts in the template DNA. J Biol Chem 278: 35791–35797PubMedGoogle Scholar
  170. 170.
    Rabik CA, Dolan ME (2007) Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev 33: 9–23PubMedGoogle Scholar
  171. 171.
    Damsma GE, Alt A, Brueckner F, Carell T, Cramer P (2007) Mechanism of transcriptional stalling at cisplatin-damaged DNA. Nat Struct Mol Biol 14: 1127–1133PubMedGoogle Scholar
  172. 172.
    Brueckner F, Hennecke U, Carell T, Cramer P (2007) CPD damage recognition by transcribing RNA polymerase II. Science 315: 859–862PubMedGoogle Scholar
  173. 173.
    Venema J, van Hoffen A, Karcagi V, Natarajan AT, van Zeeland AA, Mullenders LH (1991) Xeroderma pigmentosumcomplementation group C cells remove pyrimidine dimers selectively from the transcribed strand of active genes. Mol Cell Biol 11: 4128–4134PubMedGoogle Scholar
  174. 174.
    Troelstra C, van Gool A, de Wit J, Vermeulen W, Bootsma D, Hoeijmakers JH (1992) ERCC6, a member of the subfamily of putative helicases, is involved in Cockayne’s syndrome and preferential repair of active genes. Cell 71: 939–953PubMedGoogle Scholar
  175. 175.
    van Hoffen A, Natarajan AT, Mayne LV, van Zeeland AA, Mullenders LH, Venema J (1993) Deficient repair of the transcribed strand of active genes in Cockayne’s syndrome cells. Nucleic Acids Res 21: 5890–5895PubMedGoogle Scholar
  176. 176.
    Mayne LV, Lehmann AR (1982) Failure of RNA synthesis to recover after UV irradiation: An early defect in cells from individuals with Cockayne’s syndrome and Xeroderma pigmentosum. Cancer Res 42: 1473–1478PubMedGoogle Scholar
  177. 177.
    Andressoo JO, Hoeijmakers JH (2005) Transcription-coupled repair and premature ageing. Mutat Res 577: 179–194PubMedGoogle Scholar
  178. 178.
    Groisman R, Polanowska J, Kuraoka I, Sawada J, Saijo M, Drapkin R, Kisselev AF, Tanaka K, Nakatani Y (2003) The ubiquitin ligase activity in the DDB2 and CSA complexes is differentially regulated by the COP9 signalosome in response to DNA damage. Cell 13: 357–367Google Scholar
  179. 179.
    Citterio E, Van Den Boom V, Schnitzler G, Kanaar R, Bonte E, Kingston RE, Hoeijmakers JH, Vermeulen W (2000) ATP-dependent chromatin remodeling by the Cockayne syndrome B DNA repair-transcription-coupling factor. Mol Cell Biol 20: 7643–7653PubMedGoogle Scholar
  180. 180.
    van den Boom V, Citterio E, Hoogstraten D, Zotter A, Egly JM, van Cappellen WA, Hoeijmakers JH, Houtsmuller AB, Vermeulen W (2004) DNA damage stabilizes interaction of CSB with the transcription elongation machinery. J Cell Biol 166: 27–36PubMedGoogle Scholar
  181. 181.
    Fousteri M, Vermeulen W, van Zeeland AA, Mullenders LH (2006) Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo. Mol Cell 23: 471–482PubMedGoogle Scholar
  182. 182.
    Bregman DB, Halaban R, van Gool AJ, Henning KA, Friedberg EC, Warren SL (1996) UVinduced ubiquitination of RNA polymerase II: A novel modification deficient in itCockayne syndrome cells. Proc Natl Acad Sci USA 93: 11586–11590PubMedGoogle Scholar
  183. 183.
    Lee KB, Wang D, Lippard SJ, Sharp PA (2002) Transcription-coupled and DNA damage-dependent ubiquitination of RNA polymerase II in vitro. Proc Natl Acad Sci USA 99: 4239–4244Google Scholar
  184. 184.
    Anindya R, Aygün O, Svejstrup JQ (2007) Damage-induced ubiquitylation of human RNA polymerase II by the ubiquitin ligase Nedd4, but not Cockayne syndrome proteins or BRCA1. Mol Cell 28: 386–397PubMedGoogle Scholar
  185. 185.
    Sarker AH, Tsutakawa SE, Kostek S, Ng C, Shin DS, Peris M, Campeau E, Tainer JA, Nogales E, Cooper PK (2005) Recognition of RNA polymerase II and transcription bubbles by XPG, CSB, and TFIIH: Insights for transcription-coupled repair and Cockayne Syndrome. Mol Cell 20: 187–198PubMedGoogle Scholar
  186. 186.
    Nouspikel T, Hanawalt PC (2000) Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression. Mol Cell Biol 20: 1562–1570PubMedGoogle Scholar
  187. 187.
    Nouspikel T, Hanawalt PC (2002) DNA repair in terminally differentiated cells. DNA Rep 1: 59–75Google Scholar
  188. 188.
    Nouspikel T, Hyka-Nouspikel N, Hanawalt PC (2006) Transcription domain-associated repair in human cells. Mol Cell Biol 26: 8722–8730PubMedGoogle Scholar
  189. 189.
    Harper JW, Elledge SJ (2007) The DNA damage response: Ten years after. Mol Cell 28: 739–744PubMedGoogle Scholar
  190. 190.
    Lee JH, Paull TT (2005) ATM activation by DNA double-strand through the Mre11-Rad50-Nbs1 complex. Science 308: 551–554PubMedGoogle Scholar
  191. 191.
    Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421: 499–506PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2009

Authors and Affiliations

  • Ulrike Camenisch
    • 1
  • Hanspeter Naegeli
    • 1
  1. 1.Institute of Pharmacology and ToxicologyUniversity of Zürich-VetsuisseZürichSwitzerland

Personalised recommendations