Recognition of DNA Damage During Replication

  • Hanspeter Naegeli
Part of the Molecular Biology Intelligence Unit book series (MBIU)

Abstract

DNA lesions can be eliminated from metazoan organisms by DNA repair processes or by cell death. If DNA damage remains unrepaired and cells survive, the efficiency and fidelity of essential nuclear functions is seriously threatened. In particular, replication of damaged DNA represents a major mechanism of genetic instability.1,2 Covalent modification of DNA bases may disrupt the hydrogen bonding information and generate noninstructional sites. During subsequent DNA replication, damaged templates are unable to mediate the recruitment of complementary deoxyribonucleotides using their hydrogen-bonding pattern and, in many cases, DNA polymerases have only a 25% probability of adding the correct base. As a general rule, DNA polymerases tend to select purines, preferentially adenine residues, across such noninstructional sites.3

Keywords

Recombination Hydrocortisone Thymidine Purine Nucleoside 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Echols H, Goodman M.F. Fidelity mechanisms in DNA replication. Annu Rev Biochem 1991; 60:477–511.CrossRefGoogle Scholar
  2. 2.
    McBride TJ, Preston BD, Loeb LA. Mutagenic spectrum resulting from DNA damage by oxygen radicals. Biochemistry 1991; 30:207–213.CrossRefGoogle Scholar
  3. 3.
    Strauss BS. The “A Rule” of mutagen specificity: a consequence of DNA polymerase bypass of non-instructional lesions? BioEssays 1991;13:79–84.CrossRefGoogle Scholar
  4. 4.
    Kaufmann WK. Pathways of human cell post-replication repair. Carcinogenesis 1989; 10:1–11.CrossRefGoogle Scholar
  5. 5.
    Kaufmann WK, Rice JM, Wenk ML et al. Reversible inhibition of rat hepatocyte proliferation by hydrocortisone and its effect on cell cycle-dependent hepatocarcinogenesis by N-methyl-N-nitrosourea. Cancer Res. 1981; 41:4653–4660.Google Scholar
  6. 6.
    Kaufmann WK, Rice JM, Wenk ML et al. Cell cycle-dependent initiation of hepatocarcinogenesis in rats by methyl-(acetoxymethyl)nitrosamine. Cancer Res 1987;47:1263–1266.Google Scholar
  7. 7.
    Kaufmann WK, Rahija RJ, MacKenzie SA et al. Cell cycle-dependent initiation of hepatocarcinogenesis in rats by (±)-7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetra-hydrobenzo[a]pyrene. Cancer Res 1987; 47:3771–3775.Google Scholar
  8. 8.
    Kaufmann WK, Wilson SJ. Gl arrest and cell cycle-dependent clastogenesis in UV-irradiated human fibroblasts. Mutat. Res 1994; 314:67–76.CrossRefGoogle Scholar
  9. 9.
    Grisham JW, Greenberg DS, Kaufman DG et al. Cycle-related toxicity and transformation in 10T1/2 cells treated with N-methyl-N’-nitro-N-nitroso-guanidine. Proc Natl Acad Sci USA 1980; 77:4813–4817.CrossRefGoogle Scholar
  10. 10.
    Bertram JS, Heidelberger C. Cell cycle dependency of oncogenic transformation induced by N-methyl-N’-nitro-N-nitrosoguanidine in culture. Cancer Res 1974; 34:526–537.Google Scholar
  11. 11.
    Strauss BS. Cellular aspects of DNA repair. Adv Cancer Res 1985; 45:45–105.CrossRefGoogle Scholar
  12. 12.
    Hruszkewycz AM, Canella KA, Peltonen K et al. DNA polymerase action on benzo[a]pyrene-DNA adducts. Carcinogenesis 1992; 13:2347–2352.CrossRefGoogle Scholar
  13. 13.
    Shibutani S, Margulis LA, Geacintov NE et al. Translesional synthesis on a DNA template containing a single stereoisomer of dG-(+) or dG-(-)-anti-BPDE (7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene). Biochemistry 1993; 32:7531–7541.CrossRefGoogle Scholar
  14. 14.
    Voigt JM, Topal MD. O 6-methylguanineinduced replication blocks. Carcinogenesis 1995; 16:1775–1782.CrossRefGoogle Scholar
  15. 15.
    Moore PD, Bose KK, Rabkin SD et al. Sites of termination of in vitro DNA synthesis on ultraviolet-and N-acetylaminofluorene-treated φX174 templates by prokaryotic and eukaryotic DNA polymerases. Proc Natl Acad Sci USA 1981; 78:110–114.CrossRefGoogle Scholar
  16. 16.
    Rabkin SD, Strauss BS. A role for DNA polymerase in the specificity of nucleotide incorporation opposite N-acetylaminofluorene adducts. J Mol Biol 1984; 178:569–594.CrossRefGoogle Scholar
  17. 17.
    Woodgate R, Bridges BA, Herrera G et al. Mutagenic DNA repair in Escherichia coli. XIII. Proofreading exonuclease of DNA polymerase III holoenzyme is not operational during UV mutagenesis. Mutat Res 1987; 183:31–37.CrossRefGoogle Scholar
  18. 18.
    Shwartz H, Shavitt O, Livneh Z. The role of exonucleolytic processing and polymerase-DNA association in bypass of lesions during replication in vitro. J Biol Chem 1988; 263:18277–18285.Google Scholar
  19. 19.
    Strauss BS, Wang J. Role of DNA polymerase 3′-5′ exonuclease activity in the bypass of aminofluorene lesions in DNA. Carcinogenesis 1990; 11:2103–2109.CrossRefGoogle Scholar
  20. 20.
    Hoffmann J-S, Moustacchi E, Villani G et al. In vitro synthesis by DNA polymerase I and DNA polymerase α on single-stranded DNA containing either purine or pyrimidine monoadducts. Biochem Pharmacol 1992; 44:1123–1129.CrossRefGoogle Scholar
  21. 21.
    Hess MT, Schwitter U, Petretta M et al. DNA synthesis arrest at C4′-modified deoxyribose residues. Biochemistry 1997; in press.Google Scholar
  22. 22.
    Campbell J. Eukaryotic DNA replication. Annu Rev Biochem 1986; 55:733–772.CrossRefGoogle Scholar
  23. 23.
    DePamphilis ML. Origins of DNA replication in metazoan chromosomes. J Biol Chem 1993; 268:1–4.Google Scholar
  24. 24.
    Diller JD, Raghuraman MK. Eukaryotic replication origins: control in space and time. Trends Biochem Sci 1994; 19:320–325.CrossRefGoogle Scholar
  25. 25.
    Almouzni G, Méchali M. Assembly of spaced chromatin promoted by DNA synthesis in extracts from Xenopus eggs. EMBO J 1988; 7:665–672.Google Scholar
  26. 26.
    Krude T, Knippers R. Nucleosome assembly during complementary DNA strand synthesis in extracts from mammalian cells. J Biol Chem 1993; 268:14432–14442.Google Scholar
  27. 27.
    Navas TA, Zhou Z, Elledge SJ. DNA polymerase links the DNA replication machinery to the S phase checkpoint. Cell 1995; 80:29–39.CrossRefGoogle Scholar
  28. 28.
    Hartwell LH, Weinert TA. Checkpoints: controls that ensure the order of cell cycle events. Science 1989; 246:629–634.CrossRefGoogle Scholar
  29. 29.
    Kuerbitz SJ, Plunkett BS, Walsh WV et al. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 1992; 89:7491–7495.CrossRefGoogle Scholar
  30. 30.
    Zhou Z and Elledge SJ. DUN1 encodes a protein kinase that controls the DNA damage response in yeast. Cell 1993; 75:1119–1127.CrossRefGoogle Scholar
  31. 31.
    Lehmann AR. The relationship between pyrimidine dimers and replicating DNA in UV-irradiated human fibroblasts. Nucleic Acids Res 1979; 7:1901–1912.CrossRefGoogle Scholar
  32. 32.
    Waters R. Repair of DNA in replicating and unreplicating portions of the human genome. J Mol Biol 1979; 127:117–127.CrossRefGoogle Scholar
  33. 33.
    Vos J-M, Hanawalt PC. Processing of psoralen adducts in an active human gene: repair and replication of DNA containing monoadducts and intrastrand cross-links. Cell 1987; 50:789–799.CrossRefGoogle Scholar
  34. 34.
    Rupp WD, Howard-Flanders P. Discontinuities in the DNA synthesized in an excision-defective strain of Escherichia coli following ultraviolet irradiation. J Mol Biol 1968; 31:291–304.CrossRefGoogle Scholar
  35. 35.
    Lehmann AR, Kirk-Bell S, Arlett CF et al. Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation. Proc Natl Acad Sci USA 1975;72:219–233.CrossRefGoogle Scholar
  36. 36.
    Park SD, Cleaver JE. Postreplication repair: questions of its definition and possible alteration in xeroderma pigmentosum cell strains. Proc Natl Acad Sci USA 1979; 76:3927–3931.CrossRefGoogle Scholar
  37. 37.
    Spivak G, Hanawalt PC. Translesion DNA synthesis in the dihydrofolate reductase domain of UV-irradiated CHO cells. Biochemistry 1984; 31:6794–6800.CrossRefGoogle Scholar
  38. 38.
    Sarasin AR, Hanawalt PC. Replication of ultraviolet-irradiated simian virus 40 in monkey kidney cells. J Mol Biol 1980; 138:299–319.CrossRefGoogle Scholar
  39. 39.
    Rajagopalan M, Lu C, Woodgate R et al. (1992) Activity of the purified mutagenesis proteins UmuC, UmuD′, and RecA in replicative bypass of an abasic DNA lesion by DNA polymerase III. Proc Natl Acad Sci USA 1992; 89:10777–10781.CrossRefGoogle Scholar
  40. 40.
    O’Day CL, Burgers PMJ, Taylor JS. PCNA-induced DNA synthesis past cissyn and trans-syn-I thymine dimers by calf thymus DNA polymerase 5 in vitro. Nucleic Acids Res 1992; 20:5403–5406.CrossRefGoogle Scholar
  41. 41.
    Hoffmann J-S, Pillaire M-J, Maga G et al. DNA polymerase β bypasses in vitro a single d(GpG)-cisplatin adduct placed on codon 13 of the HRAS gene. Proc Natl Acad Sci USA 1995; 92:5356–5360.CrossRefGoogle Scholar
  42. 42.
    Hoffmann J-S, Pillaire M-J, Garcia-Estefania D et al. In vitro bypass replication of the cisplatin-d(GpG) lesion by calf thymus DNA polymerase β and human immunodeficiency virus type I reverse transcriptase is highly mutagenic. J Biol Chem 1996; 271:15386–15392.CrossRefGoogle Scholar
  43. 43.
    Morrison A, Christensen RB, Alley J et al. REV3, a yeast gene whose function is required for induced mutagenesis, is predicted to encode a non-essential DNA polymerase. J Bacteriol 1989; 171:5659–5667.Google Scholar
  44. 44.
    Nelson JR, Lawrence CW, Hinkle DC. Thymine-thymine dimer bypass by yeast DNA polymerase ζ. Science 1996; 272:1646–1649.CrossRefGoogle Scholar
  45. 45.
    Lehmann AR. Postreplication repair of DNA in ultraviolet-irradiated mammalian cells. No gaps in DNA synthesized late after ultraviolet irradiation. Eur J Biochemistry 1972; 31:438–445.CrossRefGoogle Scholar
  46. 46.
    Clarkson JM, Hewitt RR. Significance of dimers to the size of newly synthesized DNA in UV-irradiated Chinese hamster ovary cells. Biophys J 1976; 16:1155–1164.CrossRefGoogle Scholar
  47. 47.
    Meneghini R, Hanawalt P. T4-endonuclease V-sensitive sites in DNA from ultraviolet-irradiated human cells. Biochim Biophys Acta 1976; 425:428–437.CrossRefGoogle Scholar
  48. 48.
    Fujiwara Y, Tatsumi M. Low levels of DNA exchanges in normal human and xeroderma pigmentosum cells after UV irradiation. Mutat Res 1977; 43:279–290.CrossRefGoogle Scholar
  49. 49.
    Higgins NP, Kato K, Strauss B. A model for replication repair in mammalian cells. J Mol Biol 1976; 101:417–425.CrossRefGoogle Scholar
  50. 50.
    Tatsumi K, Strauss B. Production of DNA bifilarly substituted with bromodeoxyuridine in the first round of synthesis: branch migration during isolation of cellular DNA. Nucleic Acids Res 1978; 5:331–346.CrossRefGoogle Scholar
  51. 51.
    Gasser SM. Replication origins, factors and attachment sites. Curr Opin Cell Biol 1991; 3:407–413.CrossRefGoogle Scholar
  52. 52.
    Painter RB. Inhibition and recovery of DNA synthesis in human cells after exposure to ultraviolet light. Mutat Res 1985; 145:63–69.CrossRefGoogle Scholar
  53. 53.
    Griffiths TD, Ling SY. Activation of alternative sites of replicon initiation in Chinese hamster cells exposed to ultraviolet light. Mutat Res 1987; 184:39–46.CrossRefGoogle Scholar
  54. 54.
    Friedberg EC, Siede W, Cooper AJ. Cellular responses to DNA damage in yeast. In: Broach J, Jones E, Pringle J, ed. The Molecular and Cellular Biology of the Yeast Saccharomyces: Genome Dynamics, Protein Synthesis, and Energetics. Vol I. New York: Cold Spring Harbour Laboratory Press, 1991:147–192.Google Scholar
  55. 55.
    Di Caprio L, Cox BS. DNA synthesis in UV-irradiated yeast. Mutat Res 1981; 82:69–85.CrossRefGoogle Scholar
  56. 56.
    Lawrence C. The RAD6 DNA repair pathway in Saccharomyces cerevisiae: what does it do, and how does it do it? BioEssays 1994; 16:253–257.CrossRefGoogle Scholar
  57. 57.
    Lemontt JF. Pathways of ultraviolet mutability in Saccharomyces cerevisiae. II. Genetic analysis and properties of mutants resistant to ultraviolet-induced forward mutation. Mutat Res 1977; 43:179–204.CrossRefGoogle Scholar
  58. 58.
    Larimer FW, Perry JR, Hardigree AA. The REV1 gene of Saccharomyces cerevisiae: isolation, sequence, and functional analysis. J Bacteriol 1989; 171:230–237.Google Scholar
  59. 59.
    Nelson JR, Lawrence CW, Hinkle DC. Deoxycytidyl transferase activity of yeast REV1 protein. Nature 382; 382:729-731.Google Scholar
  60. 60.
    Torpey LE, Gibbs PE, Nelson J et al. Cloning and sequence of REV7, a gene whose function is required for DNA damage-induced mutagenesis in Saccharomyces cerevisiae. Yeast 1994; 10:1503–1509CrossRefGoogle Scholar
  61. 61.
    Jentsch S, McGrath JP, Varshavsky A. The yeast DNA repair gene RAD6 encodes a ubiquitin-conjugating enzyme. Nature 1987; 329:131–134.CrossRefGoogle Scholar
  62. 62.
    Montelone BA, Prakash S, Prakash L. Recombination and mutagenesis in rad6 mutants of Saccharomyces cerevisiae. Evidence for multiple functions of the RAD6 gene. Mol Gen Genet 1981; 184:410–415.CrossRefGoogle Scholar
  63. 63.
    Schwencke J, Moustacchi E. Proteolytic activities in yeast after UV irradiation. 2. Variation in proteinase levels in mutants blocked in DNA repair pathways. Mol Gen Genet 1982; 185:296–301.CrossRefGoogle Scholar
  64. 64.
    Hollingsworth RE, Ostroff RM, Klein MB et al. Molecular genetic studies of the Cdc7 protein kinase and induced mutagenesis in yeast. Genetics 1992; 132:53–62.Google Scholar
  65. 65.
    Rong L, Klein HL. Purification and characterization of the SRS2 DNA helicase of the yeast Saccharomyces cerevisiae. J Biol Chem 1993; 268:1252–1259.Google Scholar
  66. 66.
    Palladino F, Klein HL. Analysis of mitotic and meiotic defects in Saccharomyces cerevisiae SRS2 DNA helicase mutants. Genetics 1992; 132:23–37.Google Scholar
  67. 67.
    Naegeli H, Bardwell L, Friedberg EC. The DNA helicase and adenosine triphosphatase activities of yeast Rad3 protein are inhibited by DNA damage. J Biol Chem 1992; 267:392–398.Google Scholar
  68. 68.
    Naegeli H, Bardwell L, Friedberg EC. 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 1993; 32:613–621.CrossRefGoogle Scholar
  69. 69.
    Naegeli H, Modrich P, Friedberg EC. The DNA helicase activity of Rad3 protein of Saccharomyces cerevisiae and helicase II of Escherichia coli are differentially inhibited by covalent and noncovalent DNA modifications. J Biol Chem 1993; 268:10386–10392.Google Scholar
  70. 70.
    Johnson RE, Henderson ST, Petes TD et al. Saccharomyces cerevisiae RAD5-encoded DNA repair protein contains DNA helicase and zinc-binding sequence motifs and affects the stability of simple repetitive sequences in the genome. Mol Cell Biol 1992; 12:3807–3818.Google Scholar
  71. 71.
    Jones JS, Weber S, Prakash L. The Saccharomyces cerevisiae RAD18 gene encodes a protein that contains potential zinc finger domains for nucleic acid binding and a putative nucleotide binding sequence. Nucleic Acids Res 1988; 16:7119–7131.CrossRefGoogle Scholar
  72. 72.
    Koken M, Reynolds P, Bootsma D et al. Dhr6, a Drosophila homolog of the yeast DNA-repair gene RAD6. Proc Natl Acad Sci USA 1991; 88:3832–3836.CrossRefGoogle Scholar
  73. 73.
    Koken M, Reynolds P, Jaspers-Dekker I et al. Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6. Proc Natl Acad Sci USA 1991; 88:8865–8869.CrossRefGoogle Scholar
  74. 74.
    Roest HP, van Klaveren J, de Wit J et al. Inactivation of the HR6B ubiquitin-conjugating DNA repair enzyme in mice causes male sterility associated with chromatin modification. Cell 1996; 86:799–810.CrossRefGoogle Scholar
  75. 75.
    Boyd JB, Setlow RB. Characterisation of postreplication repair in mutagen-sensitive strains of Drosophila melanogaster. Genetics 1976; 84:507–526.Google Scholar
  76. 76.
    Boyd JB, Mason JM, Yamamoto AH et al. A genetic and molecular analysis of DNA repair in Drosophila. J Cell Sci 1987; Suppl 6:39–60.Google Scholar
  77. 77.
    Brown TC, Boyd JB. Postreplication repair-defective mutants of Drosophila melanogaster fall into two classes. Mol Gen Genet 1981; 183:356–362.CrossRefGoogle Scholar
  78. 78.
    Hari KL, Santerre A, Sekelsky JJ et al. The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene. Cell 1995; 82:815–821.CrossRefGoogle Scholar
  79. 79.
    Cleaver JE. Defective repair replication in xeroderma pigmentosum. Nature 1968; 218:652–656.CrossRefGoogle Scholar
  80. 80.
    Tung BS, McGregor WG, Wang YC et al. Comparison of the rate of excision of major UV photoproducts in the strands of the human HPRT gene of normal and xeroderma pigmentosum variant cells. Mutat Res 1996; 362:65–74.CrossRefGoogle Scholar
  81. 81.
    Misra RR. Vos J-M H. Defective replication of psoralen adducts detected at the gene-specific level in xeroderma pigmentosum variant cells. Mol Cell Biol 1993; 13:1002–1012.Google Scholar
  82. 82.
    Maher VM, Ouellette LM, Curren RD. Frequency of ultraviolet light-induced mutations is higher in xeroderma pigmentosum variant cells than in normal human cells. Nature 1976; 261:593–595.CrossRefGoogle Scholar
  83. 83.
    Myhr BC, Turnbull D, DiPaolo JA. Ultraviolet mutagenesis of normal and xeroderma pigmentosum variant human fibroblasts. Mutat Res 1979; 63:341–353.Google Scholar
  84. 84.
    Wang YC, Maher VM, McCormick JJ. Xeroderma pigmentosum variant cells are less likely than normal cells to incorporate dAMP opposite photoproducts during replication of UV-irradiated plasmids. Proc Natl Acad Sci USA 1991; 88:7810–7814.CrossRefGoogle Scholar
  85. 85.
    Wang YC, Maher VM, Mitchell DL et al. Evidence from mutation spectra that the UV hypermutability of xeroderma pigmentosum variant cells reflects abnormal, error-prone replication on a template containing photoproducts. Mol Cell Biol 1993; 13:4276–4283.Google Scholar
  86. 86.
    Raha M, Wang G, Seidman MM et al. Mutagenesis by third-strand-directed psoralen adducts in repair-deficient cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. Proc Natl Acad Sci USA 1996; 93:2941–2946.CrossRefGoogle Scholar
  87. 87.
    Carty MP, Hauser J, Levine AS et al. Replication and mutagenesis of UV-damaged DNA templates in human and monkey cell extracts. Mol Cell Biol 1993; 13:533–542.Google Scholar
  88. 88.
    Thomas DC, Kunkel TA. Replication of UV-irradiated DNA in human cell extracts: evidence for mutagenic bypass of pyrimidine dimers. Proc Natl Acad Sci USA 1993; 90:7744–7748.CrossRefGoogle Scholar
  89. 89.
    Carty MP, El-Saleh S, Zernik-Kobak M et al. Analysis of mutations induced by replication of UV-damaged plasmid DNA in HeLa cell extract. Environ Molecul Mutagen 1995; 26:139–146.CrossRefGoogle Scholar
  90. 90.
    Thomas DC, Nguyen DC, Piegorsch WW et al. Relative probability of mutagenic translesion synthesis on the leading and lagging strands during replication of UV-irradiated DNA in a human cell extract. Biochemistry 1993; 32:11476–11482.CrossRefGoogle Scholar
  91. 91.
    Thomas DC, Svoboda DL, Vos JMH et al. Strand specificity of mutagenic bypass replication of DNA containing psoralen monoadducts in a human cell extract. Mol Cell Biol 1996; 16:2537–2544.Google Scholar
  92. 92.
    Thomas DC, Veaute X, Kunkel TA et al. Mutagenic replication in human cell extracts of DNA containing site-specific N-2-acetylaminofluorene adducts. Proc Natl Acad Sci USA 1994; 91:7752–7756CrossRefGoogle Scholar

Copyright information

© R.G. Landes Company 1997

Authors and Affiliations

  • Hanspeter Naegeli
    • 1
  1. 1.Institute of Pharmacology and ToxicologyUniversity of Zürich-TierspitalZürichSwitzerland

Personalised recommendations