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. 1982 Feb 25;10(4):1203–1213. doi: 10.1093/nar/10.4.1203

Inhibitors of repair DNA synthesis.

A R Collins, S Squires, R T Johnson
PMCID: PMC320519  PMID: 6803229

Abstract

We have measured repair DNA synthesis in UV-irradiated normal human fibroblasts, grown to a defined state of quiescence in order to avoid the problem of discriminating repair from replicative DNA synthesis. We have assessed the effects of various DNA synthesis inhibitors on repair. Inhibition of repair synthesis by hydroxyurea, 1-beta-D-arabinofuranosylcytosine and aphidicolin is associated with the ability to accumulate DNA breaks due to enzymic incision at DNA damage sites; the inhibition by novobiocin is in accord with its known ability to block incision.

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Selected References

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  1. Berger N. A., Kurohara K. K., Petzold S. J., Sikorski G. W. Aphidicolin inhibits eukaryotic DNA replication and repair --- implications for involvement of DNA polymerase alpha in both processes. Biochem Biophys Res Commun. 1979 Jul 12;89(1):218–225. doi: 10.1016/0006-291x(79)90966-5. [DOI] [PubMed] [Google Scholar]
  2. Brandt W. N., Flamm W. G., Bernheim N. J. The value of hydroxyurea in assessing repair synthesis of DNA in HeLa cells. Chem Biol Interact. 1972 Oct;5(5):327–339. doi: 10.1016/0009-2797(72)90072-5. [DOI] [PubMed] [Google Scholar]
  3. Burke J. F., Duff P. M., Pearson C. K. Effect of drugs on deoxyribonucleic acid synthesis in isolated mammalian cell nuclei. Comparison with partially purified deoxyribonucleic acid polymerases. Biochem J. 1979 Mar 15;178(3):621–626. doi: 10.1042/bj1780621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clarkson J. M. Enhancement of repair replication in mammalian cells by hydroxyurea. Mutat Res. 1978 Nov;52(2):273–284. doi: 10.1016/0027-5107(78)90148-3. [DOI] [PubMed] [Google Scholar]
  5. Cleaver J. E. Repair replication of mammalian cell DNA: effects of compounds that inhibit DNA synthesis or dark repair. Radiat Res. 1969 Feb;37(2):334–348. [PubMed] [Google Scholar]
  6. Collins A. R., Johnson R. T. Repair and survival after UV in quiescent and proliferating Microtus agrestis cells: different rates of incision and different dependence on DNA precursor supply. J Cell Physiol. 1979 Apr;99(1):125–137. doi: 10.1002/jcp.1040990114. [DOI] [PubMed] [Google Scholar]
  7. Collins A., Johnson R. Novobiocin; an inhibitor of the repair of UV-induced but not X-ray-induced damage in mammalian cells. Nucleic Acids Res. 1979 Nov 10;7(5):1311–1320. doi: 10.1093/nar/7.5.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. DULBECCO R., VOGT M. One-step growth curve of Western equine encephalomyelitis virus on chicken embryo cells grown in vitro and analysis of virus yields from single cells. J Exp Med. 1954 Feb;99(2):183–199. doi: 10.1084/jem.99.2.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dicioccio R. A., Chadha K., Sahai Srivastava B. I. Inhibition of herpes simplex virus-induced DNA polymerase, cellular DNA polymerase alpha, and virus production by aphidicolin. Biochim Biophys Acta. 1980 Sep 19;609(2):224–231. doi: 10.1016/0005-2787(80)90233-6. [DOI] [PubMed] [Google Scholar]
  10. Dunn W. C., Regan J. D. Inhibition of DNA excision repair in human cells by arabinofuranosyl cytosine: effect on normal and xeroderma pigmentosum cells. Mol Pharmacol. 1979 Mar;15(2):367–374. [PubMed] [Google Scholar]
  11. Hanaoka F., Kato H., Ikegami S., Oashi M., Yamada M. Aphidicolin does inhibit repair replication in HeLa cells. Biochem Biophys Res Commun. 1979 Mar 30;87(2):575–580. doi: 10.1016/0006-291x(79)91833-3. [DOI] [PubMed] [Google Scholar]
  12. Ikegami S., Taguchi T., Ohashi M., Oguro M., Nagano H., Mano Y. Aphidicolin prevents mitotic cell division by interfering with the activity of DNA polymerase-alpha. Nature. 1978 Oct 5;275(5679):458–460. doi: 10.1038/275458a0. [DOI] [PubMed] [Google Scholar]
  13. Lehmann A. R., Stevens S. A rapid procedure for measurement of DNA repair in human fibroblasts and for complementation analysis of xeroderma pigmentosum cells. Mutat Res. 1980 Jan;69(1):177–190. doi: 10.1016/0027-5107(80)90187-6. [DOI] [PubMed] [Google Scholar]
  14. Mattern M. R., Scudiero D. A. Dependence of mammalian DNA synthesis on DNA supercoiling. III. Characterization of the inhibition of replicative and repair-type DNA synthesis by novobiocin and nalidixic acid. Biochim Biophys Acta. 1981 Apr 27;653(2):248–258. doi: 10.1016/0005-2787(81)90160-x. [DOI] [PubMed] [Google Scholar]
  15. Pedrali-Noy G., Spadari S. Aphidicolin allows a rapid and simple evaluation of DNA-repair synthesis in damaged human cells. Mutat Res. 1980 May;70(3):389–394. doi: 10.1016/0027-5107(80)90029-9. [DOI] [PubMed] [Google Scholar]
  16. Reichard P. Control of deoxyribonucleotide synthesis in vitro and in vivo. Adv Enzyme Regul. 1972;10:3–16. doi: 10.1016/0065-2571(72)90003-9. [DOI] [PubMed] [Google Scholar]
  17. Schor S. L., Johnson R. T., Waldren C. A. Changes in the organization of chromosomes during the cell cycle: response to ultraviolet light. J Cell Sci. 1975 May;17(3):539–565. doi: 10.1242/jcs.17.3.539. [DOI] [PubMed] [Google Scholar]
  18. Smith C. A., Hanawalt P. C. Repair replication in human cells. Simplified determination utilizing hydroxyurea. Biochim Biophys Acta. 1976 May 19;432(3):336–347. doi: 10.1016/0005-2787(76)90143-x. [DOI] [PubMed] [Google Scholar]
  19. Snyder R. D., Carrier W. L., Regan J. D. Application of arabinofuranosyl cytosine in the kinetic analysis and quantitation of DNA repair in human cells after ultraviolet irradiation. Biophys J. 1981 Aug;35(2):339–350. doi: 10.1016/S0006-3495(81)84793-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Snyder R. D., Regan J. D. Aphidicolin inhibits repair of DNA in UV-irradiated human fibroblasts. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1088–1094. doi: 10.1016/0006-291x(81)90730-0. [DOI] [PubMed] [Google Scholar]
  21. Stefanini M., Dalpra L., Zei G., Giorgi R., Falaschi A., Nuzzo F. Incorporation of (3H)thymidine stimulated by ultraviolet radiation into human fibroblast cultures. Mutat Res. 1976 Feb;34(2):313–326. doi: 10.1016/0027-5107(76)90136-6. [DOI] [PubMed] [Google Scholar]
  22. Sutton W. D. A crude nuclease preparation suitable for use in DNA reassociation experiments. Biochim Biophys Acta. 1971 Jul 29;240(4):522–531. doi: 10.1016/0005-2787(71)90709-x. [DOI] [PubMed] [Google Scholar]
  23. Trosko J. E., Yager J. D. A sensitive method to measure physical and chemical carcinogen-induced "unscheduled DNA synthesis" in rapidly dividing eukaryotic cells. Exp Cell Res. 1974 Sep;88(1):47–55. doi: 10.1016/0014-4827(74)90616-8. [DOI] [PubMed] [Google Scholar]
  24. Waters R. Aphidicolin: an inhibitor of DNA repair in human fibroblasts. Carcinogenesis. 1981;2(8):795–797. doi: 10.1093/carcin/2.8.795. [DOI] [PubMed] [Google Scholar]

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