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Mammalian DNA Repair and the Cellular DNA Polymerases

  • Chapter
DNA Damage and Repair

Part of the book series: Contemporary Cancer Research ((CCR))

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Abstract

Genomic DNA is damaged by various physical and chemical agents during the life of an organism. For faithful reproduction and preservation of genomic DNA, damaged DNA sites must be repaired, and organisms have several DNA repair pathways that are vital in maintaining genome stability. Each individual DNA repair pathway (i.e., error-free repair, base excision repair, nucleotide excision repair, and so forth) is generally similar throughout nature, and this concept of conservation has been invaluable in rapidly advancing the mammalian DNA repair field. Several examples of DNA polymerase-independent “error-free repair” are well known, including photolyase reversal of UV damage and methyltransferase reversal of alkylation damage. In the various excision repair pathways, all of which involve some form of DNA polymerase-mediated gap-filling, the damaged site in DNA is first recognized and excised, the excision gap is tailored to allow gap-filling DNA synthesis, the nucleotide sequence is restored through DNA synthesis, and finally the phosphodiester backbone is ligated. Excision repair of damaged DNA is, therefore, a sequential multistep process. The specific enzyme(s) involved in an individual step may depend on the type of DNA lesion being repaired and the DNA structure/sequence context surrounding the lesion. Since resynthesis of a DNA sequence after excision of damaged DNA is catalyzed by a DNA polymerase, these enzymes clearly play a central role in DNA repair and hence in genomic stability.

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References

  1. Abbotts, J., D. N. SenGupta, B. Zmudzka, S. G. Widen, B. Notario, and S. H. Wilson. 1988. Expression of human DNA polymerase beta in Escherichia coli and characterization of the recombinant enzyme. Biochemistry 27: 901–909.

    Article  PubMed  CAS  Google Scholar 

  2. Albert, W., F. Grummt, U. Hubscher, and S. H. Wilson. 1982. Structural homology among calf thymus a-polymerase polypeptides. Nucleic Acids Res. 10: 935–946.

    Article  PubMed  CAS  Google Scholar 

  3. Anderson, R. S., C. B. Lawrence, S. H. Wilson, and K. L. Beattie. 1987. Genetic relatedness of DNA polymerase beta and terminal deoxynucleotidyltransferase. Gene 60: 163–173.

    Article  PubMed  CAS  Google Scholar 

  4. Aoyagi, N., S. Matsuoka, A. Furunobu, A. Matsukage, and K. Sakaguchi. 1994. Drosophila DNA polymerase delta. Purification and characterization. J. Biol. Chem. 269: 60456050.

    Google Scholar 

  5. Bambara, R. A. and C. B. Jessee. 1991. Properties of DNA polymerases S and c, and their roles in eukaryotic DNA replication. Biochim. Biophys. Acta 1088: 11–24.

    Article  PubMed  CAS  Google Scholar 

  6. Bambara, R. A., T. W. Myers, and R. D. Sabatino. 1990. DNA polymerase S, in The Eukaryotic Nucleus: Molecular Biochemistry and Macromolecular Assemblies ( Strauss, P. and S. Wilson, eds.), Telford Press, Caldwell, NJ, pp. 69–94.

    Google Scholar 

  7. Baril, E. F., O. E. Brown, M. D. Jenkins, and J. Laszlo. 1971. Deoxyribonucleic acid polymerase with rat liver ribosomes and smooth membranes, Purification and properties of the enzymes. Biochemistry 10: 1981–1992.

    Article  PubMed  CAS  Google Scholar 

  8. Basu, A. K. and J. M. Essigmann. 1988. Site-specifically modified oligodeoxynucleotides as probes for the structural and biological effects of DNA-damaging agents. Chem. Res. Toxicol. 1: 1–18.

    Article  PubMed  CAS  Google Scholar 

  9. Bauer, G. A. and P. M. Burgers. 1988. Protein-protein interactions of yeast DNA polymerase III with mammalian and yeast proliferating cell nuclear antigen (PCNA)/cyclin. Biochim. Biophys. Acta 951: 274–279.

    Article  PubMed  CAS  Google Scholar 

  10. Beard, W. A., W. P. Osheroff, R. Prasad, M. Jaju, M. R. Sawaya, T. G. Wood, J. Kraut, T. A. Kunkel, and S. H. Wilson. 1996. Enzyme-DNA interactions required for efficient nucleotide incorporation and discrimination in human DNA polymerase 13. J. Biol. Chem. 271: 12,141–12, 144.

    Google Scholar 

  11. Bensch, K. G., S. Tanaka, S. Z. Hu, T. S. Wang, and D. Korn. 1982. Intracellular localization of human DNA polymerase a with monoclonal antibodies. J. Biol. Chem. 257: 8391–8396.

    PubMed  CAS  Google Scholar 

  12. Berger, N. A., K. K. Kurohara, S. J. Petzoid, and G. W. Sikorski. 1979. Aphidicolin inhibits eukaryotic DNA replication and repair-implications for involvement of DNA polymerase a in both processes. Biochem. Biophys. Res. Commun. 89: 218–225.

    Article  PubMed  CAS  Google Scholar 

  13. Biade, S., R. W. Sobol, S. H. Wilson, and Y. Matsumoto. Impairment of proliferating cell nuclear antigen (PCNA)-dependent base excision repair on linear DNA. Submitted.

    Google Scholar 

  14. Blank, A., B. Kim, and L. A. Loeb. 1994. DNA polymerase S is required for base excision repair of DNA methylation damage in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 91: 9047–9051.

    Article  CAS  Google Scholar 

  15. Bohr, V. A., D. H. Phillips, and P. C. Hanawalt. 1987. Heterogeneous DNA damage and repair in the mammalian genome. Cancer Res. 47: 6426–6436.

    PubMed  CAS  Google Scholar 

  16. Brill, S. J. and B. Stillman. 1989. Yeast replication factor-A functions in the unwinding of the SV40 origin of DNA replication. Nature 342: 92–95.

    Article  PubMed  CAS  Google Scholar 

  17. Budd, M. E. and J. L. Campbell. 1995. DNA polymerases required for repair of UV-induced damage in Saccharomyces cerevisiae. Mol. Cell. Biol. 15: 2173–2179.

    CAS  Google Scholar 

  18. Burger, R. M., A. R. Berkowitz, J. Peisach, and S. B. Horowitz. 1980. Origin of malondialdehyde from DNA degraded by Fe(II)-bleomycin. J. Biol. Chem. 255: 11,83211, 838.

    Google Scholar 

  19. Burgers, P. M. 1989. Eukaryotic DNA polymerases a and S: conserved properties and interactions, from yeast to mammalian cells. Prog. Nucleic Acid Res. Mol. Biol. 37: 235–280.

    Article  PubMed  CAS  Google Scholar 

  20. Burgers, P. M. 1991. Saccharomyces cerevisiae replication factor C. II. Formation and activity of complexes with the proliferating cell nuclear antigen and with DNA polymerases S and c. J. Biol. Chem. 266: 22,698–22,706.

    Google Scholar 

  21. Byrnes, J. J. 1984. Structural and functional properties of DNA polymerase S from rabbit bone marrow. Mol. Cell. Biochem. 62: 13–24.

    Article  PubMed  CAS  Google Scholar 

  22. Byrnes, J. J. 1985. Differential inhibitors of DNA polymerases a and S. Biochem. Biophys. Res. Commun. 132: 628–634.

    Article  PubMed  CAS  Google Scholar 

  23. Byrnes, J. J., K. M. Downey, B. L. Black, and A. G. So. 1976. A new mammalian DNA polymerase with 3’ to 5’ exonuclease activity: DNA polymerase S. Biochemistry 15: 28172823.

    Google Scholar 

  24. Cannizzaro, L. A., F. J. Bollum, K. Huebner, C. M. Croce, L. C. Cheung, X. Xu, B. K. Hecht, F. Hecht, and L. M. S. Chang. 1988. Chromosome sublocalization of a cDNA for human DNA polymerase ß to 8p11-p12. Cytogenet. Cell. Genet. 47: 121–124.

    Article  PubMed  CAS  Google Scholar 

  25. Castellot, J. J., Jr., M. R. Miller, D. M. Lehtomaki, and A. B. Pardee. 1979. Comparison of DNA replication and repair enzymology using permeabilized baby hamster kidney cells. J. Biol. Chem. 254: 6904–6908.

    PubMed  CAS  Google Scholar 

  26. Chang, L. M. S. and F. J. Bollum. 1971. Low molecular weight deoxyribonucleic acid polymerase in mammalian cells. J. Biol. Chem. 246: 5835–5837.

    PubMed  CAS  Google Scholar 

  27. Chen, K.-H., F. M. Yakes, D. K. Srivastava, R. K. Singhal, R. W. Sobol, J. K. Horton, B. Van Houten, and S. H. Wilson. Oxidative stress inducing agents up-regulate base excision repair in mouse cell lines. Nucleic Acids Res.,in press.

    Google Scholar 

  28. Chen, Y.-C., E. W. Bohn, S. R. Planck, and S. H. Wilson. 1979. Mouse DNA polymerase alpha: subunit structure and identification of a species with associated exonuclease. J. Biol. Chem. 254: 11,678–11, 687.

    Google Scholar 

  29. Chui, G. and S. Linn. 1995. Further characterization of HeLa DNA polymerase epsilon. J. Biol. Chem. 270: 7799–7808.

    Article  PubMed  CAS  Google Scholar 

  30. Chung, D. W., J. Zhang, C. K. Tan, E. W. Davie, A. G. So, and K. M. Downey. 1991. Primary structure of the catalytic subunit of human DNA polymerase 8 and chromosomal location of the gene. Proc. Natl. Acad. Sci. USA 88: 11,197–11, 201.

    Google Scholar 

  31. Ciarrocchi, G., J. G. Jose, and S. Linn. 1979. Further characterization of a cell-free system for measuring replicative and repair DNA synthesis with cultured human fibroblasts and evidence for the involvement of DNA polymerase a in DNA repair. Nucleic Acids Res. 7: 1205–1219.

    Article  PubMed  CAS  Google Scholar 

  32. Cotterill, S. M., M. E. Reyland, L. A. Loeb, and I. R. Lehman. 1987. A cryptic proofreading 3’ 5’ exonuclease associated with the polymerase subunit of the DNA polymeraseprimase from Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 84: 5635–5639.

    Article  CAS  Google Scholar 

  33. Cripps-Wolfman, J., E. C. Henshaw, and R. A. Bambara. 1989. Alterations in the phosphorylation and activity of DNA polymerase a correlate with the change in replicative DNA synthesis as quiescent cells re-enter the cell cycle. J. Biol. Chem. 264: 19,47819, 486.

    Google Scholar 

  34. Crute, J. J., A. F. Wahl, and R. A. Bambara. 1986. Purification and characterization of two new high molecular weight forms of DNA polymerase S. Biochemistry 25: 26–36.

    Article  CAS  Google Scholar 

  35. Cullman, G., R. Hindges, M. W. Berchtold, and U. Hübscher. 1993. Cloning of a mouse cDNA encoding DNA polymerase delta: refinement of the homology boxes. Gene 134: 191–200.

    Article  Google Scholar 

  36. Da Costa, L. T., B. Liu, W. El-Deiry, S. R. Hamilton, K. W. Kinzler, B. Vogelstein, S. Markowitz, J. K. Willson, A. de la Chapelle, K. M. Downey, and A. G. So. 1995. Polymerase delta variants in RER colorectal tumors [letter]. Nat. Genet. 9: 10, 11.

    Google Scholar 

  37. Di Giuseppe, J. A. and S. L. Dresler. 1989. Bleomycin-induced DNA repair synthesis in permeable human fibroblasts: mediation of long-patch and short-patch repair by distinct DNA polymerases. Biochemistry 28: 9515–9520.

    Article  Google Scholar 

  38. Dresler, S. L. 1984. Comparative enzymology of ultraviolet-induced DNA repair synthesis and semiconservative DNA replication in permeable diploid human fibroblasts. J. Biol. Chem. 259: 13,947–13, 952.

    Google Scholar 

  39. Dresler, S. L. and M. G. Frattini. 1986. DNA replication and UV-induced DNA repair synthesis in human fibroblasts are much less sensitive than DNA polymerase a to inhibition by butylphenyl-deoxyguanosine triphosphate. Nucleic Acids Res. 14: 7093–7102.

    Article  PubMed  CAS  Google Scholar 

  40. Dresler, S. L. and M. G. Frattini. 1988. Analysis of butylphenyl-guanine, butylphenyldeoxyguanosine, and butylphenyl-deoxyguanosine triphosphate inhibition of DNA replication and ultraviolet-induced DNA repair synthesis using permeable human fibroblasts. Biochem. Pharmacol. 37: 1033–1037.

    Article  PubMed  CAS  Google Scholar 

  41. Dresler, S. L. and K. S. Kimbro. 1987.2’, 3’-Dideoxythymidine 5’-triphosphate inhibition of DNA replication and ultraviolet-induced DNA repair synthesis in human cells: evidence for involvement of DNA polymerase 6. Biochemistry 26: 2664–2668.

    Google Scholar 

  42. Dresler, S. L. and M. W. Lieberman. 1983. Identification of DNA polymerases involved in DNA excision repair in diploid human fibroblasts. J. Biol. Chem. 258: 9990–9994.

    PubMed  CAS  Google Scholar 

  43. Dresler, S. L., M. G. Frattini, and R. M. Robinson-Hill. 1988. In situ enzymology of DNA replication and ultraviolet-induced DNA repair synthesis in permeable human cells. Biochemistry 27: 7247–7254.

    Article  PubMed  CAS  Google Scholar 

  44. Fisher, P. A., T. S. Wang, and D. Korn. 1979. Enzymological characterization of DNA polymerase a. Basic catalytic properties processivity, and gap utilization of the homogeneous enzyme from human KB cells. J. Biol. Chem. 254: 6128–6137.

    PubMed  CAS  Google Scholar 

  45. Fortini, P., B. Pascucci, R. W. Sobol, S. H. Wilson, and E. Dogliotti. Different DNA polymerases are involved in the short-and long-patch base excision repair in mammalian cells. Biochemistry 37: 3575–3580.

    Google Scholar 

  46. Friedberg, E. C. 1992. Xeroderma pigmentosum, Cockayne’s syndrome, helicases, and DNA repair: what’s the relationship? Cell 71: 887–889.

    Article  PubMed  CAS  Google Scholar 

  47. Friedberg, E. C., G. C. Walker, and W. Siede. 1995. In DNA Repair and Mutagenesis, American Society for Microbiology, Washington, DC, pp. 317–365.

    Google Scholar 

  48. Frosina, G., P. Fortini, O. Rossi, F. Carrozzino, A. Abbondandolo, and E. Dogliotti. 1994. Repair of abasic sites by mammalian cell extracts. Biochem. J. 304: 699–705.

    PubMed  CAS  Google Scholar 

  49. Frosina, G., P. Fortini, O. Rossi, F. Carrozzino, G. Raspaglio, L. S. Cox, D. P. Lane, A. Abbondandolo, and E. Dogliotti. 1996. Two pathways for base excision repair in mammalian cells. J. Biol. Chem. 271: 9573–9578.

    Article  PubMed  CAS  Google Scholar 

  50. Fry, M. and L. A. Loeb. 1986. Animal Cell DNA Polymerases. CRC, Boca Raton, FL.

    Google Scholar 

  51. Goscin, L. P. and J. J. Byrnes. 1982. DNA polymerase 6: one peptide, two activities. Biochemistry 21: 2513–2518.

    Article  PubMed  CAS  Google Scholar 

  52. Goulian, M. and C. J. Heard. 1989. Intact DNA polymerase a/primase from mouse cells: purification and structure. J. Biol. Chem. 264: 19,407–19, 415.

    Google Scholar 

  53. Hanaoka, F., H. Kato, S. Ikegami, M. Ohashi, and M. Yamada. 1979. Aphidicolin does inhibit repair replication in HeLa cells. Biochem. Biophys. Res. Commun. 87: 575–580.

    Article  PubMed  CAS  Google Scholar 

  54. Hanawalt, P. C., P. K. Cooper, A. K. Ganesan, and C. A. Smith. 1979. DNA repair in bacteria and mammalian cells. Ann. Rev. Biochem. 48: 783–836.

    Article  PubMed  CAS  Google Scholar 

  55. Hindges, R. and U. Hübscher. 1997. DNA polymerase 6, an essential enzyme for DNA transactions. Biol. Chem. 378: 345–362.

    PubMed  CAS  Google Scholar 

  56. Holmes, J., S. J. Clark, and P. Modrich. 1990. Strand-specific mismatch correction in nuclear extracts of human and Drosophila melanogaster cell lines. Proc. Natl. Acad. Sci. USA 87: 5837–5841.

    Article  PubMed  CAS  Google Scholar 

  57. Huberman, J. A. 1981. New views of the biochemistry of eukaryotic DNA replication revealed by aphidicolin, an unusual inhibitor of DNA polymerase a. Cell 23: 647, 648.

    Google Scholar 

  58. Ikegami, S., T. Taguchi, M. Ohashi, M. Oguro, H. Nagano, and Y. Mano. 1978. Aphidicolin prevents mitotic cell division by interfering with the activity of DNA polymerase-a. Nature (Lond.) 275: 458–460.

    Article  CAS  Google Scholar 

  59. Ilsley, D. D., S. H. Lee, W. H. Miller, and R. D. Kuchta. 1995. Acyclic guanosine analogs inhibit DNA polymerases alpha, delta, and epsilon with very different potencies and have unique mechanisms of action. Biochemistry 34: 2504–2510.

    Article  PubMed  CAS  Google Scholar 

  60. Jasko, M. V., D. G. Semizarov, L. S. Victorova, Mozzherin, A. A. Krayevsky, and M. K. Kukhanova. 1995. New modified substrates for discriminating between human DNA polymerases alpha and epsilon. FEBS Lett. 357: 23–26.

    Article  PubMed  CAS  Google Scholar 

  61. Jenkins, T. M., J. K Saxena, A. Kumar, S. H. Wilson, and E. J. Ackerman. 1992. DNA polymerase f3 and DNA synthesis in Xenopus oocytes and in a nuclear extract. Science 258: 475–478.

    Article  PubMed  CAS  Google Scholar 

  62. Keeney, S. and S. Linn. 1990. A critical review of permeabilized cell systems for studying mammalian DNA repair. Mutat. Res. 236: 239–252.

    Article  PubMed  CAS  Google Scholar 

  63. Kesti, T. and J. E. Syvaoja. 1991. Identification and tryptic cleavage of the catalytic core of HeLa and calf thymus DNA polymerase epsilon. J. Biol. Chem. 266: 6336–6341.

    PubMed  CAS  Google Scholar 

  64. Kesti, T., F. Hannele, and J. E. Syväoja. 1993. Molecular cloning of the catalytic subunit of human DNA polymerase epsilon. J. Biol. Chem. 268: 10,238–10, 245.

    Google Scholar 

  65. Keyse, S. M. and R. M. Tyrrell. 1985. Excision repair in permeable arrested human skin fibroblasts damaged by UV (254 nm) radiation: evidence that a-and f3-polymerases act sequentially at the repolymerization step. Muta. Res. 146: 109–119.

    Article  CAS  Google Scholar 

  66. Khan, N. N., G. E. Wright, L. W. Dudycz, and N. C. Brown. 1984. Butyllphenyl dGTP: a selective and potent inhibitor of mammalian DNA polymerase a. Nucleic Acids Res. 12: 3695–3706.

    Article  PubMed  CAS  Google Scholar 

  67. Klungland, A. and T. Lindahl. 1997. Second pathway for completion of human DNA base excision-repair: reconstitution with purified proteins and requirement for DNase IV (FEN 1). EMBO J. 16: 3341–3348.

    Article  PubMed  CAS  Google Scholar 

  68. Kolodner, R. D. 1995. Mismatch repair: mechanisms and relationship to cancer susceptibility. Trends. Biochem. Sci. 20: 391–397.

    Article  Google Scholar 

  69. Kornberg, A. and T. Baker. 1991. DNA Replication. Freeman, New York.

    Google Scholar 

  70. Kubota, Y., R. A. Nash, A. Klungland, P. Schar, D. Barnes, and T. Lindahl. 1996. Reconstitution of DNA base excision-repair with purified human proteins: interaction between DNA polymerase ß and the XRCC1 protein. EMBO J. 15: 6662–6670.

    PubMed  CAS  Google Scholar 

  71. Kumar, A., J. Abbotts, E. Karawya, and S. H. Wilson. 1990. Identification and properties of the catalytic domain of mammalian DNA polymerase beta. Biochemistry 29: 71567159.

    Google Scholar 

  72. Lan, S. Y. and M. J. Smerdon. 1985. A nonuniform distribution of excision repair synthesis in nucleosome core DNA. Biochemistry 24: 7771–7783.

    Article  PubMed  CAS  Google Scholar 

  73. Lee, M. Y. W. T., and N. L. Toomey. 1987. Human placental DNA polymerase 8: identification of a 170-kilodalton polypeptide by activity staining and immunoblotting. Biochemistry 26: 1076–1085.

    Article  PubMed  CAS  Google Scholar 

  74. Lee, M. Y. W. T., C.-K. Tan, A. G. So, and K. M. Downey. 1980. Purification of deoxyribonucleic acid polymerase S from calf thymus: partial characterization of physical properties. Biochemistry 19: 2096–2101.

    Article  PubMed  CAS  Google Scholar 

  75. Lee, M. Y. W. T., C.-K. Tan, K. M. Downey and A. G. So. 1984. Further studies on calf thymus DNA polymerase S purified to homogeneity by a new procedure. Biochemistry 23: 1906–1913.

    Article  PubMed  CAS  Google Scholar 

  76. Lee, M. Y., Y. Q. Jiang, S. J. Zhang, and N. L. Toomey. 1991. Characterization of human DNA polymerase delta and its immunochemical relationships with DNA polymerase alpha and epsilon. J. Biol. Chem. 266: 2423–2429.

    PubMed  CAS  Google Scholar 

  77. Lee, S. H., Z. Q. Pan, A. D. Kwong, P. M. Burgers, and J. Hurwitz. 1991. Synthesis of DNA by DNA polymerase s in vitro. J. Biol. Chem. 266: 22,707–22, 717.

    Google Scholar 

  78. Lehman, I. R. and L. S. Kaguni. 1989. DNA polymerase a. J. Biol. Chem. 264: 42654268.

    Google Scholar 

  79. Lewis, W., R. R. Meyer, J. F. Simpson, J. M. Colacino, and F. W. Perrino. 1994. Mammalian DNA polymerases alpha, beta, gamma, delta, and epsilon incorporate fialuridine (FIAU) monophosphate into DNA and are inhibited competitively by FIAU Triphosphate. Biochemistry 33: 14, 620–14, 624.

    Google Scholar 

  80. Linn, S. 1991. How many pois does it take to replicate nuclear DNA? Cell 66: 185–187.

    Article  PubMed  CAS  Google Scholar 

  81. Loeb, L. A., P. K. Liu, and M. Fry. 1986. DNA polymerase-alpha: enzymology, function, fidelity, and mutagenesis. Prog. Nucleic Acid Res. Mol. Biol. 33: 57–110.

    Article  PubMed  CAS  Google Scholar 

  82. Maga, G. and U. Hübscher. 1995. DNA polymerase epsilon interacts with proliferating cell nuclear antigen in primer recognition and elongation. Biochemistry 34: 891–901.

    Article  PubMed  CAS  Google Scholar 

  83. Matsukage, A., E. W. Bohn, and S. H. Wilson. 1974. Multiple forms of DNA polymerase in mouse myeloma. Proc. Natl. Acad. Sci. USA 71: 578–582.

    Article  PubMed  CAS  Google Scholar 

  84. Matsumoto, T., T. Eki., and J. Hurwitz. 1990. Studies on the initiation and elongation reactions in the simian virus 40 DNA replication system. Proc. Natl. Acad. Sci. USA 87: 9712–9716.

    CAS  Google Scholar 

  85. Matsumoto, Y. and K. Kim. 1995. Excision of deoxyribose phosphate residues by DNA polymerase ß during DNA repair. Science 269: 699–702.

    Article  PubMed  CAS  Google Scholar 

  86. Matsumoto, Y., K. Kim, and D. F. Bogenhagen. 1994. Proliferating cell nuclear antigen-dependent abasic site repair in Xenopus laevis oocytes: an alternating pathway of base excision repair. Mol. Cell. Biol. 14: 6187–6197.

    Article  PubMed  CAS  Google Scholar 

  87. McBride, O. W., C. A. Kozak, and S. H. Wilson. 1990. Mapping of the gene for DNA polymerase ß to mouse chromosome 8. Cytogenet. Cell Genet. 53: 108–111.

    Article  PubMed  CAS  Google Scholar 

  88. Mellon, I., V. A. Bohr, C. A. Smith, and P. C. Hanawalt. 1986. Preferential DNA repair of an active gene in human cells. Proc. Natl. Acad. Sci. USA 83: 8878–8882.

    Article  PubMed  CAS  Google Scholar 

  89. Miller, M. R. and D. N. Chinault. 1982. Evidence that DNA polymerases a and ß participate differentially in DNA repair synthesis induced by different agents. J. Biol. Chem. 257: 46–49.

    PubMed  CAS  Google Scholar 

  90. Miller, M. R. and D. N. Chinault. 1982. The roles of DNA polymerases a, ß, y and in DNA repair synthesis induced in hamster and human cells by different DNA damaging agents. J. Biol. Chem. 257: 10,204–10, 209.

    Google Scholar 

  91. Modrich, P. 1994. Mismatch repair, genetic stability, and cancer. Science 266: 1959, 1960.

    Google Scholar 

  92. Modrich, P. 1991. Mechanisms and biological effects of mismatch repair. Ann. Rev. Genet. 25: 229–253.

    Article  PubMed  CAS  Google Scholar 

  93. Morrison, A., H. Araki, A. B. Clark, R. K. Hamatake, and A. Sugino. 1990. A third essential DNA polymerase in S. Cerevisiae. Cell 62: 1143–1151.

    CAS  Google Scholar 

  94. Mosbaugh, D. W. and S. Linn. 1983. Excision repair and DNA synthesis with a combination of HeLa DNA polymerase ß and DNase V. J. Biol. Chem. 258: 108–118.

    PubMed  CAS  Google Scholar 

  95. Mosbaugh, D. W. and S. Linn. 1984. Gap-filling DNA synthesis by HeLa DNA polymerase alpha in an in vitro base excision DNA repair scheme. J. Biol. Chem. 259: 10,24710, 251.

    Google Scholar 

  96. Mullen, G. P. and S. H. Wilson. 1997. Repair activity in DNA polymerases: a structurally conserved helix-hairpin-helix motif in base excision repair enzymes and in DNA polymerase ß. Biochemistry 36: 4713–4717.

    Article  PubMed  CAS  Google Scholar 

  97. Mullen, G. P., Antuch, W., Maciejewski, M. W., Prasad, R., and S. H. Wilson. 1997. Insights into the mechanism of the f3-elimination catalyzed by the N-terminal domain of DNA polymerase ß. Tetrahedron 53(35): 12, 057–12, 066.

    Google Scholar 

  98. Narayan, S., F. He, and S. H. Wilson. 1996. Activation of the human DNA polymerase ß promoter by a DNA-alkylating agent through induced phosphorylation of CREB-1. J. Biol. Chem. 271: 18,508–18, 513.

    Google Scholar 

  99. Navas, T. A., Z. Zhou, and S. J. Elledge. 1995. DNA polymerase epsilon links the DNA replication machinery to the S phase checkpoint. Cell 80: 29–39.

    Article  PubMed  CAS  Google Scholar 

  100. Nealon, K., I. D. Nicholl, and M. K. Kenny. 1996. Characterization of the DNA polymerase requirement of human base excision repair. Nucleic Acids Res. 24: 3763–3770.

    Article  PubMed  CAS  Google Scholar 

  101. Nicholl, I. D., K. Nealon, and M. K. Kenny. 1997. Reconstitution of human base excision repair with purified proteins. Biochemistry 36: 7557–7566.

    Article  PubMed  CAS  Google Scholar 

  102. Niranjanakumari, S. and K. P. Gopinathan. 1993. Isolation and characterization of DNA polymerase epsilon from the silk glands of Bombyx mori. J. Biol. Chem. 268: 15,55715, 564.

    Google Scholar 

  103. Nishida, C., P. Reinhard, and S. Linn. 1988. DNA repair synthesis in human fibroblasts requires DNA polymerase delta. J. Biol. Chem. 263: 501–510.

    PubMed  CAS  Google Scholar 

  104. Ottiger, H.-P. and U. Hübscher. 1984. Mammalian DNA polymerase a holoenzymes with possible functions at the leading and lagging strand of the replication fork. Proc. Natl. Acad. Sci. USA 81: 3993–3997.

    Article  PubMed  CAS  Google Scholar 

  105. Pelletier, H. M. R. Sawaya, W. Wolfle, S. H. Wilson, and J. Kraut. 1996. A structural basis for metal ion mutagenicity and nucleotide selectivity in human DNA polymerase. Biochemistry 35: 12,762–12,777.

    Google Scholar 

  106. Perrino, F. W. and L. A. Loeb. 1989. Proofreading by the s subunit of Escherichia coli DNA polymerase III increases the fidelity of calf thymus DNA polymerase a. Proc. Natl. Acad. Sci. USA 86: 3085–3088.

    Article  PubMed  CAS  Google Scholar 

  107. Piersen, C. E., R. Prasad, S. H. Wilson, and R. S. Lloyd. 1996. Evidence for an imino intermediate in the DNA polymerase ß deoxyribose phosphate excision reaction. J. Biol. Chem. 271: 17,811–17, 815.

    Google Scholar 

  108. Planck, S. R., K. Tanabe, and S. H. Wilson. 1980. Distinction between mouse DNA polymerases a and 13 by tryptic peptide mapping. Nucleic Acids Res. 8: 2771–2782.

    Article  PubMed  CAS  Google Scholar 

  109. Prasad, R., R. K. Singhal, D. K. Srivastava, A. E. Tomkinson, and S. H. Wilson. 1996. Specific interaction of DNA polymerase 13 and DNA ligase I in a multiprotein base excision repair complex from bovine testis. J. Biol. Chem. 271: 16,000–16, 007.

    Google Scholar 

  110. Prasad, R., S. G. Widen, R. K. Singhal, J. Watkins, L. Prakash, and S. H. Wilson. 1993. Yeast open reading frame YCR14C encodes a DNA polymerase 13-like enzyme. Nucleic Acids Res. 21: 5301–5307.

    Article  PubMed  CAS  Google Scholar 

  111. Randahl, H., G. C. Elliott, and S. Linn. 1988. DNA-repair reactions by purified HeLa DNA polymerases and exonucleases. J. Biol. Chem. 263: 12,228–12, 234.

    Google Scholar 

  112. Regan, J. D. and R. B. Setlow. 1974. Two forms of repair in the DNA of human cells damaged by chemical carcinogens and mutagens. Cancer Res. 34: 3318–3325.

    PubMed  CAS  Google Scholar 

  113. Sawaya, M. R., H. Pelletier, A. Kumar, S. H. Wilson, and J. Kraut. 1994. Crystal structure of rat DNA polymerase 13 reveals a conserved polymerase catalytic site. Science 264: 2930–2935.

    Article  Google Scholar 

  114. Seeberg, E., L. Eide, and M. Bj, râs. 1995. The base excision repair pathway. Trends Biochem. Sci. 20: 391–397.

    Article  CAS  Google Scholar 

  115. Seki, S. and T. Oda. 1988. An exonuclease possibly involved in the initiation of repair of bleomycin-damaged DNA in mouse ascites sarcoma cells. Carcinogenesis 9: 2239–2244.

    Article  PubMed  CAS  Google Scholar 

  116. SenGupta, D. N., B. Z. Zmudzka, P. Kumar, F. Cobianchi, J. Skowronski, and S. H. Wilson. 1986. Sequence of human DNA polymerase 13 mRNA obtained through cDNA cloning. Biochem. Biophys. Res. Commun. 136: 341–347.

    Google Scholar 

  117. Shivji, M. K., V. N. Podust, U. Hübscher, and R. D. Wood. 1995. Nucleotide excision repair DNA synthesis by DNA polymerase epsilon in the presence of PCNA, RFC, and RPA. Biochemistry 34: 5011–5017.

    Article  PubMed  CAS  Google Scholar 

  118. Siegal, G., J. J. Turchi, T. W. Myers, and R. A. Bambara. 1992. A 5’ to 3’ exonuclease functionally interacts with calf DNA polymerase e. Proc. Natl. Acad. Sci. USA 89: 9377–9381.

    Article  CAS  Google Scholar 

  119. Siedlecki, J. A., J. Szyszko, I Pietrzykowska, and B. Zmudzka. 1980. Evidence implying DNA polymerase beta function in excision repair. Nucleic Acids Res. 8: 361–375.

    Article  PubMed  CAS  Google Scholar 

  120. Singhal, R. K. and S. H. Wilson. 1993. Short gap-filling synthesis by DNA polymerase ß is processive. J. Biol. Chem. 268: 15,906–15, 911.

    Google Scholar 

  121. Singhal, R. K., R. Prasad, and S. H. Wilson. 1995. DNA polymerase ß conducts the gap-filling step in uracil-initiated base excision repair in a bovine testis nuclear extract. J. Biol. Chem. 270: 949–957.

    Article  PubMed  CAS  Google Scholar 

  122. Skarnes, W., P. Bonin, and E. Baril. 1986. Exonuclease activity associated with a multiprotein form of HeLa cell DNA polymerase a. Purification and properties of the exonuclease. J. Biol. Chem. 261: 6629–6636.

    PubMed  CAS  Google Scholar 

  123. Smith, C. A. and D. S. Okumoto. 1984. Nature of DNA repair synthesis resistant to inhibitors of polymerase a in human cells. Biochemistry 23: 1383–1391.

    Article  PubMed  CAS  Google Scholar 

  124. So, A. G. and K. M. Downey. 1988. Mammalian DNA polymerases a and S: current status in DNA replication. Biochemistry 27: 4591–4595.

    Article  PubMed  CAS  Google Scholar 

  125. Sobol, R. W., J. K. Horton, R. Kühn, H. Gu, R. K. Singhal, R. Prasad, K. Rajewsky, and S. H. Wilson. 1996. Requirement of mammalian DNA polymerase-ß in base-excision repair. Nature 379: 183–186.

    Article  PubMed  CAS  Google Scholar 

  126. Spadari, S., F. Sala, and G. Pedrali-Noy. 1984. Aphidicolin and eukaryotic DNA synthesis. Adv. Exp. Med. Biol. 179: 169–181.

    PubMed  CAS  Google Scholar 

  127. Srivastava, D. K., T. Y. Rawson, S. D. Showalter, and S. H. Wilson. 1995. Phorbol ester abrogates up-regulation of DNA polymerase ß by DNA alkylating agents in Chinese hamster ovary cells. J. Biol. Chem. 270: 16,402–16, 408.

    Google Scholar 

  128. Sweasy, J. B., M. Chen, and L. A. Loeb. 1995. DNA polymerase beta can substitute for DNA polymerase I in the initiation of plasmid DNA replication. J. Bacteriol. 177: 2923–2925.

    PubMed  CAS  Google Scholar 

  129. Syvaoja, J. and S. Linn. 1989. Characterization of a large form of DNA polymerase S from HeLa cells that is insensitive to proliferating cell nuclear antigen. J. Biol. Chem. 264: 2489–2497.

    PubMed  CAS  Google Scholar 

  130. Syvaoja, J., S. Suomensaari, C. Nishida, J. S. Goldsmith, and S. Linn. 1990. DNA polymerases a, S, and e: three distinct enzymes from HeLa cells. Proc. Natl. Acad. Sci. USA 87: 6664–6668.

    Article  PubMed  CAS  Google Scholar 

  131. Szpirer, J., F. Pedeutour, T. Kesti, M. Riviere, J. E. Syvaoja, C. Turc-Carel, and C. Szpirer. 1994. Localization of the gene for DNA polymerase epsilon (POLE) to human chromosome 12824.3 and rat chromosome 12 by somatic cell hybrid panels and fluorescence in situ hybridization. Genomics 20: 223–226.

    Article  PubMed  CAS  Google Scholar 

  132. Tan, C.-K., C. Castillo, A. G. So, and K. M. Downey. 1986. An auxiliary protein for DNA polymerase S from fetal calf thymus. J. Biol. Chem. 261: 12,310–12, 316.

    Google Scholar 

  133. Tanaka, S., S. Z. Hu, T. S.-F. Wang, and D. Korn. 1982. Preparation and preliminary characterization of monoclonal antibodies against human DNA polymerase a. J. Biol. Chem. 257: 8386–8390.

    PubMed  CAS  Google Scholar 

  134. Thomas, D. C., J. D. Roberts, and T. A. Kunkel. 1991. Heteroduplex repair in extracts of human HeLa cells. J. Biol. Chem. 266: 3744–3751.

    PubMed  CAS  Google Scholar 

  135. Tsurimoto, T. and B. Stillman. 1991. Replication factors required for SV40 DNA replication in vitro. II. DNA structure specific recognition primer template junction by eukaryotic DNA polymerases and their accessory factors. J. Biol. Chem. 266: 1950–1960.

    PubMed  CAS  Google Scholar 

  136. Tsurimoto, T. and B. Stillman. 1991. Replication factors required for SV40 DNA replication in vitro. II. Switching of DNA polymerase alpha and delta during initiation of leading and lagging strand synthesis. J. Biol. Chem. 266: 1961–1968.

    PubMed  CAS  Google Scholar 

  137. Tsurimoto, T., T. Melendy, and B. Stillman. 1990. Sequential initiation of lagging and leading strand synthesis by two different polymerase complexes at the SV40 DNA replication origin. Nature (Lond.) 346: 534–539.

    Google Scholar 

  138. Tuusa, J., L. Uitto, and J. E. Syvaoja. 1995. Human DNA polymerase epsilon is expressed during cell proliferation in a manner characteristic of replicative DNA polymerases. Nucleic Acids Res. 23: 2178–2183.

    Article  PubMed  CAS  Google Scholar 

  139. Umar, A., A. B. Buermeyer, J. A. Simon, D. C. Thomas, A. B. Clark, R. M. Liskay, and T. A. Kunkel. 1996. Requirement for PCNA in DNA mismatch repair at a step preceding DNA resynthesis. Cell 87: 65–73.

    Article  PubMed  CAS  Google Scholar 

  140. Wahl, A. F., A. M. Geis, B. H. Spain, S. W. Wong, D. K. Korn, and T. S.-F. Wang. 1988. Gene expression of human DNA polymerase a during cell proliferation and the cell cycle. Mol. Cell. Biol. 8: 5016–5025.

    PubMed  CAS  Google Scholar 

  141. Wahl, A. F., J. J. Crute, R. D. Sabatino, J. B. Bodner, R. L. Marraccino, L. W. Harwell, E. M. Lord, and R. A. Bambara. 1986. Properties of two forms of DNA polymerase 8 from calf thymus. Biochemistry 25: 7821–7827.

    Article  PubMed  CAS  Google Scholar 

  142. Wang, T. S.-F. 1991. Eukaryotic DNA polymerases. Ann. Rev. Biochem. 60: 513–552.

    Article  PubMed  CAS  Google Scholar 

  143. Wang, T. S.-F., S. Z. Hu, and D. Korn. 1984. DNA primase from KB cells. Characterization of a primase activity tightly associated with immunoaffinity-purified DNA polymerase-a. J. Biol. Chem. 259: 1854–1865.

    PubMed  CAS  Google Scholar 

  144. Wang, T. S.-F. and D. Korn. 1980. Reactivity of KB cell deoxyribonucleic acid polymerases a and 13 with nicked and gapped deoxyribonucleic acid. Biochemistry 19: 1782–1790.

    Article  PubMed  CAS  Google Scholar 

  145. Wang, T. S.-F., B. E. Pearson, H. A. Suomalainen, T. Mohandas, L. J. Shapiro, J. Schroder, and D. Korn. 1985. Assignment of the gene for human DNA polymerase a to the X chromosome. Proc. Natl. Acad. Sci. USA 82: 5270–5274.

    Article  PubMed  CAS  Google Scholar 

  146. Wang, Z., X. Wu, and E. C. Friedberg. 1993. DNA repair synthesis during base excision repair in vitro is catalyzed by DNA polymerase s and is influenced by DNA polymerase a and 8 in Saccharomyces cerevisiae. Mol. Cell. Biol. 13: 1051–1058.

    CAS  Google Scholar 

  147. Weinberg, D. H., K. L. Collins, P. Simancek, A. Russo, M. S. Wold, D. M. Virshup, and T. J. Kelly. 1990. Reconstitution of simian virus 40 DNA replication with purified proteins. Proc. Natl. Acad. Sci. USA 87: 8692–8696.

    Article  PubMed  CAS  Google Scholar 

  148. Weissbach, A., A. Schlabach, B. Fridlender, and A. Bolden. 1971. A DNA polymerase from human cells. Nature (Lond.), New Biol. 231: 167–170.

    CAS  Google Scholar 

  149. Wiebauer, K. and J. Jiricny. 1990. Mismatch-specific thymine DNA glycosylase and DNA polymerase beta mediate the correction of G. T mispairs in nuclear extracts from human cells. Proc. Natl. Acad. Sci. USA 87: 5842–5845.

    Article  PubMed  CAS  Google Scholar 

  150. Wilson, S., J. Abbotts, and S. Widen. 1988. Progress toward molecular biology of DNA polymerase ß. Biochim. Biophys. Acta 949: 149–157.

    Article  PubMed  CAS  Google Scholar 

  151. Wintersberger, E. 1974. Deoxyribonucleic acid polymerases from yeast; further purification and characterization of DNA-dependent DNA polymerases A and B. Eur. J. Biochem. 50: 41–47.

    Article  PubMed  CAS  Google Scholar 

  152. Wong, S. W., A. F. Wahl, P.-M. Yuan, N. Arai, B. E. Pearson, K.-I. Arai, D. Korn, M. W. Hunkapiller, and T. S.-F. Wang. 1988. Human DNA polymerase a gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases. EMBO J. 7: 37–47.

    Google Scholar 

  153. Wright, G. E., U. Hübscher, N. N. Khan, F. Focher and A. Verri. 1994. Inhibitor analysis of calf thymus DNA polymerases alpha, delta and epsilon. FEBS Lett. 3411: 128–130.

    Article  Google Scholar 

  154. Zeng, X. R., H. Hao, Y. Jiang, and M. Y. Lee. 1994. Regulation of human DNA polymerase delta during the cell cycle. J. Biol. Chem. 269: 24,027–24, 033.

    Google Scholar 

  155. Zeng, X. R., Y. Jiang, S. J. Zhang, H. Hao, and M. Y. Lee. 1994. DNA polymerase delta is involved in the cellular response to UV damage in human cells. J. Biol. Chem. 269: 13,748–13, 751.

    Google Scholar 

  156. Zhang, P., I. Frugulhetti, Y. Jiang, G. L. Holt, R. C. Condit, and M. Y. Lee. 1995. Expression of the catalytic subunit of human DNA polymerase delta in mammalian cells using a vaccinia virus vector system. J. Biol. Chem. 270: 7993–7998.

    Article  PubMed  CAS  Google Scholar 

  157. Zhang, S. J., X. R. Zhang, P. Zhang, N. L. Toomey, R. Y. Chuang, L. S. Chang, and M. Y. Lee. 1995. A conserved region in the amino terminus of DNA polymerase delta is involved in proliferating cell nuclear antigen binding. J. Biol. Chem. 270: 7988–7992.

    Article  PubMed  CAS  Google Scholar 

  158. Zmudzka, B. Z., A. Fornace, Jr., J. Collins, and S. H. Wilson. 1988. Characterization of DNA polymerase ß mRNA: cell-cycle and growth response in cultured human cells. Nucleic Acids Res. 16: 9587–9596.

    Article  PubMed  CAS  Google Scholar 

  159. Zmudzka, B. Z., D. SenGupta, A. Matsukage, F. Cobianchi, P. Kumar, and S. H. Wilson. 1986. Structure of rat DNA polymerase ß revealed by partial amino acid sequencing and cDNA cloning. Proc. Natl. Acad. Sci. USA 83: 5106–5110.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Samuel H. Wilson
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  2. Rakesh K. Singhal
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Editors and Affiliations

  1. University of New Mexico, Albuquerque, NM, USA

    Jac A. Nickoloff

  2. Signal Pharmaceuticals, San Diego, CA, USA

    Merl F. Hoekstra

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Wilson, S.H., Singhal, R.K. (1998). Mammalian DNA Repair and the Cellular DNA Polymerases. In: Nickoloff, J.A., Hoekstra, M.F. (eds) DNA Damage and Repair. Contemporary Cancer Research. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-455-9_11

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  • DOI: https://doi.org/10.1007/978-1-59259-455-9_11

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