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. 1990 Aug;125(4):813–819. doi: 10.1093/genetics/125.4.813

Mus308 Mutants of Drosophila Exhibit Hypersensitivity to DNA Cross-Linking Agents and Are Defective in a Deoxyribonuclease

J B Boyd 1, K Sakaguchi 1, P V Harris 1
PMCID: PMC1204107  PMID: 2397884

Abstract

Mutagen-sensitive strains that identify 16 different Drosophila genes have been screened for alterations in DNA metabolic enzymes. A characteristic defect in an acid-active deoxyribonuclease was observed in strains carrying the six available mutant alleles of the mus308 gene. Since that enzyme is detected at normal levels in a mutant strain that is deficient in the previously identified enzymes DNase 1 and DNase 2, it represents a new Drosophila nuclease that is designated Nuclease 3. The mus308 mutants were originally distinguished from all other mutagen-sensitive mutants of Drosophila because they exhibit hypersensitivity to the DNA cross-linking agent nitrogen mustard without expressing a concurrent sensitivity to the monofunctional agent methyl methanesulfonate. Further observations of hypersensitivity to the mutagens trimethylpsoralen, diepoxybutane and cis-platinum now establish a more general sensitivity of these mutants to agents capable of generating DNA cross-links. In spite of the hypersensitivity of the mus308 mutants to DNA cross-linking agents, the initial incision step of DNA cross-link repair is normal in mus308 cells as assayed by the alkaline elution procedure. The Drosophila mus308 mutants show promise of providing a useful model for analogous defects in other organisms including man.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Averbeck D., Papadopoulo D., Moustacchi E. Repair of 4,5',8-trimethylpsoralen plus light-induced DNA damage in normal and Fanconi's anemia cell lines. Cancer Res. 1988 Apr 15;48(8):2015–2020. [PubMed] [Google Scholar]
  2. Boyd J. B., Golino M. D., Nguyen T. D., Green M. M. Isolation and characterization of X-linked mutants of Drosophila melanogaster which are sensitive to mutagens. Genetics. 1976 Nov;84(3):485–506. doi: 10.1093/genetics/84.3.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Boyd J. B., Golino M. D., Shaw K. E., Osgood C. J., Green M. M. Third-chromosome mutagen-sensitive mutants of Drosophila melanogaster. Genetics. 1981 Mar-Apr;97(3-4):607–623. doi: 10.1093/genetics/97.3-4.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boyd J. B., Mason J. M., Yamamoto A. H., Brodberg R. K., Banga S. S., Sakaguchi K. A genetic and molecular analysis of DNA repair in Drosophila. J Cell Sci Suppl. 1987;6:39–60. doi: 10.1242/jcs.1984.supplement_6.3. [DOI] [PubMed] [Google Scholar]
  5. Brown T. C., Boyd J. B. Abnormal recovery of DNA replication in ultraviolet-irradiated cell cultures of Drosophila melanogaster which are defective in DNA repair. Mol Gen Genet. 1981;183(2):363–368. doi: 10.1007/BF00270641. [DOI] [PubMed] [Google Scholar]
  6. Cimino G. D., Gamper H. B., Isaacs S. T., Hearst J. E. Psoralens as photoactive probes of nucleic acid structure and function: organic chemistry, photochemistry, and biochemistry. Annu Rev Biochem. 1985;54:1151–1193. doi: 10.1146/annurev.bi.54.070185.005443. [DOI] [PubMed] [Google Scholar]
  7. Detwiler C., MacIntyre R. A genetic and developmental analysis of an acid deoxyribonuclease in Drosophila melanogaster. Biochem Genet. 1978 Dec;16(11-12):1113–1134. doi: 10.1007/BF00484532. [DOI] [PubMed] [Google Scholar]
  8. Fornace A. J., Jr, Little J. B. DNA crosslinking induced by x-rays and chemical agents. Biochim Biophys Acta. 1977 Aug 16;477(4):343–355. doi: 10.1016/0005-2787(77)90253-2. [DOI] [PubMed] [Google Scholar]
  9. Hama-Inaba H., Sato K., Moustacchi E. Survival and mutagenic responses of mitomycin C-sensitive mouse lymphoma cell mutants to other DNA cross-linking agents. Mutat Res. 1988 Sep;194(2):121–129. doi: 10.1016/0167-8817(88)90014-4. [DOI] [PubMed] [Google Scholar]
  10. Harris P. V., Boyd J. B. Excision repair in Drosophila. Analysis of strand breaks appearing in DNA of mei-9 mutants following mutagen treatment. Biochim Biophys Acta. 1980 Nov 14;610(1):116–129. doi: 10.1016/0005-2787(80)90061-1. [DOI] [PubMed] [Google Scholar]
  11. Henriques J. A., Moustacchi E. Isolation and characterization of pso mutants sensitive to photo-addition of psoralen derivatives in Saccharomyces cerevisiae. Genetics. 1980 Jun;95(2):273–288. doi: 10.1093/genetics/95.2.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Mason J. M., Green M. M., Shaw K. E., Boyd J. B. Genetic analysis of X-linked mutagen-sensitive mutants of Drosophila melanogaster. Mutat Res. 1981 May;81(3):329–343. doi: 10.1016/0027-5107(81)90120-2. [DOI] [PubMed] [Google Scholar]
  13. Papadopoulo D., Averbeck D., Moustacchi E. The fate of 8-methoxypsoralen-photoinduced DNA interstrand crosslinks in Fanconi's anemia cells of defined genetic complementation groups. Mutat Res. 1987 Nov;184(3):271–280. doi: 10.1016/0167-8817(87)90026-5. [DOI] [PubMed] [Google Scholar]
  14. Rawlings C. J., Roberts J. J. Walker rat carcinoma cells are exceptionally sensitive to cis-diamminedichloroplatinum(II) (cisplatin) and other difunctional agents but not defective in the removal of platinum-DNA adducts. Mutat Res. 1986 Sep;166(2):157–168. doi: 10.1016/0167-8817(86)90014-3. [DOI] [PubMed] [Google Scholar]
  15. Roberts J. J., Friedlos F., Scott D., Ormerod M. G., Rawlings C. J. The unique sensitivity of Walker rat tumour cells to difunctional agents is associated with a failure to recover from inhibition of DNA synthesis and increased chromosome damage. Mutat Res. 1986 Sep;166(2):169–181. doi: 10.1016/0167-8817(86)90015-5. [DOI] [PubMed] [Google Scholar]
  16. Robson C. N., Hickson I. D. Genetic analysis of mitomycin-C-sensitive mutants of a Chinese hamster ovary cell line. Mutat Res. 1986 Nov;163(2):201–208. doi: 10.1016/0027-5107(86)90049-7. [DOI] [PubMed] [Google Scholar]
  17. Smith P. D., Snyder R. D., Dusenbery R. L. Isolation and characterization of repair-deficient mutants of Drosophila melanogaster. Basic Life Sci. 1980;15:175–188. doi: 10.1007/978-1-4684-3842-0_12. [DOI] [PubMed] [Google Scholar]
  18. Snyder R. D., Smith P. D. Mutagen sensitivity of Drosophila melanogaster. V. Identification of second chromosomal mutagen sensitive strains. Mol Gen Genet. 1982;188(2):249–255. doi: 10.1007/BF00332683. [DOI] [PubMed] [Google Scholar]
  19. Van Houten B., Gamper H., Holbrook S. R., Hearst J. E., Sancar A. Action mechanism of ABC excision nuclease on a DNA substrate containing a psoralen crosslink at a defined position. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8077–8081. doi: 10.1073/pnas.83.21.8077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zdzienicka M. Z., Simons J. W. Mutagen-sensitive cell lines are obtained with a high frequency in V79 Chinese hamster cells. Mutat Res. 1987 Jun;178(2):235–244. doi: 10.1016/0027-5107(87)90274-0. [DOI] [PubMed] [Google Scholar]
  21. Zwelling L. A., Kohn K. W., Ross W. E., Ewig R. A., Anderson T. Kinetics of formation and disappearance of a DNA cross-linking effect in mouse leukemia L1210 cells treated with cis- and trans-diamminedichloroplatinum(II). Cancer Res. 1978 Jun;38(6):1762–1768. [PubMed] [Google Scholar]

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