Skip to main content
PMC home page
Genetics logoLink to Genetics
. 1995 Oct;141(2):619–627. doi: 10.1093/genetics/141.2.619

The Drosophila Meiotic Recombination Gene Mei-9 Encodes a Homologue of the Yeast Excision Repair Protein Rad1

J J Sekelsky 1, K S McKim 1, G M Chin 1, R S Hawley 1
PMCID: PMC1206761  PMID: 8647398

Abstract

Meiotic recombination and DNA repair are mediated by overlapping sets of genes. In the yeast Saccharomyces cerevisiae, many genes required to repair DNA double-strand breaks are also required for meiotic recombination. In contrast, mutations in genes required for nucleotide excision repair (NER) have no detectable effects on meiotic recombination in S. cerevisiae. The Drosophila melanogaster mei-9 gene is unique among known recombination genes in that it is required for both meiotic recombination and NER. We have analyzed the mei-9 gene at the molecular level and found that it encodes a homologue of the S. cerevisiae excision repair protein Rad1, the probable homologue of mammalian XPF/ERCC4. Hence, the predominant process of meiotic recombination in Drosophila proceeds through a pathway that is at least partially distinct from that of S. cerevisiae, in that it requires an NER protein. The biochemical properties of the Rad1 protein allow us to explain the observation that mei-9 mutants suppress reciprocal exchange without suppressing the frequency of gene conversion.

Full Text

The Full Text of this article is available as a PDF (1.9 MB).

Selected References

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

  1. Alani E., Reenan R. A., Kolodner R. D. Interaction between mismatch repair and genetic recombination in Saccharomyces cerevisiae. Genetics. 1994 May;137(1):19–39. doi: 10.1093/genetics/137.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  3. Baker B. S., Carpenter A. T. Genetic analysis of sex chromosomal meiotic mutants in Drosophilia melanogaster. Genetics. 1972 Jun;71(2):255–286. doi: 10.1093/genetics/71.2.255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baker B. S., Carpenter A. T., Ripoll P. The Utilization during Mitotic Cell Division of Loci Controlling Meiotic Recombination and Disjunction in DROSOPHILA MELANOGASTER. Genetics. 1978 Nov;90(3):531–578. doi: 10.1093/genetics/90.3.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baker B. S., Gatti M., Carpenter A. T., Pimpinelli S., Smith D. A. Effects of recombination-deficient and repair-deficient loci on meiotic and mitotic chromosome behavior in Drosophila melanogaster. Basic Life Sci. 1980;15:189–208. doi: 10.1007/978-1-4684-3842-0_13. [DOI] [PubMed] [Google Scholar]
  6. Banga S. S., Bloomquist B. T., Brodberg R. K., Pye Q. N., Larrivee D. C., Mason J. M., Boyd J. B., Pak W. L. Cytogenetic characterization of the 4BC region on the X chromosome of Drosophila melanogaster: localization of the mei-9, norpA and omb genes. Chromosoma. 1986;93(4):341–346. doi: 10.1007/BF00327593. [DOI] [PubMed] [Google Scholar]
  7. Biggerstaff M., Szymkowski D. E., Wood R. D. Co-correction of the ERCC1, ERCC4 and xeroderma pigmentosum group F DNA repair defects in vitro. EMBO J. 1993 Sep;12(9):3685–3692. doi: 10.1002/j.1460-2075.1993.tb06043.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Boyd J. B., Golino M. D., Setlow R. B. The mei-9 alpha mutant of Drosophila melanogaster increases mutagen sensitivity and decreases excision repair. Genetics. 1976 Nov;84(3):527–544. doi: 10.1093/genetics/84.3.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Carpenter A. T., Sandler L. On recombination-defective meiotic mutants in Drosophila melanogaster. Genetics. 1974 Mar;76(3):453–475. doi: 10.1093/genetics/76.3.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cleaver J. E. It was a very good year for DNA repair. Cell. 1994 Jan 14;76(1):1–4. doi: 10.1016/0092-8674(94)90165-1. [DOI] [PubMed] [Google Scholar]
  12. Curtis D., Clark S. H., Chovnick A., Bender W. Molecular analysis of recombination events in Drosophila. Genetics. 1989 Jul;122(3):653–661. doi: 10.1093/genetics/122.3.653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dicaprio L., Hastings P. J. Post-meiotic segregation in strains of Saccharomyces cerevisiae unable to excise pyrimidine dimers. Mutat Res. 1976 Oct;37(1):137–140. doi: 10.1016/0027-5107(76)90061-0. [DOI] [PubMed] [Google Scholar]
  15. Fishman-Lobell J., Haber J. E. Removal of nonhomologous DNA ends in double-strand break recombination: the role of the yeast ultraviolet repair gene RAD1. Science. 1992 Oct 16;258(5081):480–484. doi: 10.1126/science.1411547. [DOI] [PubMed] [Google Scholar]
  16. Game J. C., Zamb T. J., Braun R. J., Resnick M., Roth R. M. The Role of Radiation (rad) Genes in Meiotic Recombination in Yeast. Genetics. 1980 Jan;94(1):51–68. doi: 10.1093/genetics/94.1.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Goyon C., Lichten M. Timing of molecular events in meiosis in Saccharomyces cerevisiae: stable heteroduplex DNA is formed late in meiotic prophase. Mol Cell Biol. 1993 Jan;13(1):373–382. doi: 10.1128/mcb.13.1.373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Graf U., Vogel E., Biber U. P., Würgler F. E. Genetic control of mutagen sensitivity in Drosophila melanogaster: a new allele at the mei-9 locus on the X-chromosome. Mutat Res. 1979 Jan;59(1):129–133. doi: 10.1016/0027-5107(79)90199-4. [DOI] [PubMed] [Google Scholar]
  19. Habraken Y., Sung P., Prakash L., Prakash S. Holliday junction cleavage by yeast Rad1 protein. Nature. 1994 Oct 6;371(6497):531–534. doi: 10.1038/371531a0. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Henikoff S., Henikoff J. G. Amino acid substitution matrices from protein blocks. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915–10919. doi: 10.1073/pnas.89.22.10915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Klein H. L. Different types of recombination events are controlled by the RAD1 and RAD52 genes of Saccharomyces cerevisiae. Genetics. 1988 Oct;120(2):367–377. doi: 10.1093/genetics/120.2.367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kramer B., Kramer W., Williamson M. S., Fogel S. Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes. Mol Cell Biol. 1989 Oct;9(10):4432–4440. doi: 10.1128/mcb.9.10.4432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Meselson M. S., Radding C. M. A general model for genetic recombination. Proc Natl Acad Sci U S A. 1975 Jan;72(1):358–361. doi: 10.1073/pnas.72.1.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nag D. K., Petes T. D. Physical detection of heteroduplexes during meiotic recombination in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1993 Apr;13(4):2324–2331. doi: 10.1128/mcb.13.4.2324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pflugfelder G. O., Schwarz H., Roth H., Poeck B., Sigl A., Kerscher S., Jonschker B., Pak W. L., Heisenberg M. Genetic and molecular characterization of the optomotor-blind gene locus in Drosophila melanogaster. Genetics. 1990 Sep;126(1):91–104. doi: 10.1093/genetics/126.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pirrotta V. Vectors for P-mediated transformation in Drosophila. Biotechnology. 1988;10:437–456. doi: 10.1016/b978-0-409-90042-2.50028-3. [DOI] [PubMed] [Google Scholar]
  28. Prakash S., Prakash L., Burke W., Montelone B. A. Effects of the RAD52 Gene on Recombination in SACCHAROMYCES CEREVISIAE. Genetics. 1980 Jan;94(1):31–50. doi: 10.1093/genetics/94.1.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Prakash S., Sung P., Prakash L. DNA repair genes and proteins of Saccharomyces cerevisiae. Annu Rev Genet. 1993;27:33–70. doi: 10.1146/annurev.ge.27.120193.000341. [DOI] [PubMed] [Google Scholar]
  30. Rayssiguier C., Thaler D. S., Radman M. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature. 1989 Nov 23;342(6248):396–401. doi: 10.1038/342396a0. [DOI] [PubMed] [Google Scholar]
  31. Rubin G. M., Spradling A. C. Genetic transformation of Drosophila with transposable element vectors. Science. 1982 Oct 22;218(4570):348–353. doi: 10.1126/science.6289436. [DOI] [PubMed] [Google Scholar]
  32. Rödel C., Kirchhoff S., Schmidt H. The protein sequence and some intron positions are conserved between the switching gene swi10 of Schizosaccharomyces pombe and the human excision repair gene ERCC1. Nucleic Acids Res. 1992 Dec 11;20(23):6347–6353. doi: 10.1093/nar/20.23.6347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Schiestl R. H., Prakash S. RAD1, an excision repair gene of Saccharomyces cerevisiae, is also involved in recombination. Mol Cell Biol. 1988 Sep;8(9):3619–3626. doi: 10.1128/mcb.8.9.3619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schmidt H., Kapitza-Fecke P., Stephen E. R., Gutz H. Some of the swi genes of Schizosaccharomyces pombe also have a function in the repair of radiation damage. Curr Genet. 1989 Aug;16(2):89–94. doi: 10.1007/BF00393400. [DOI] [PubMed] [Google Scholar]
  35. Schwacha A., Kleckner N. Identification of joint molecules that form frequently between homologs but rarely between sister chromatids during yeast meiosis. Cell. 1994 Jan 14;76(1):51–63. doi: 10.1016/0092-8674(94)90172-4. [DOI] [PubMed] [Google Scholar]
  36. Smoller D. A., Petrov D., Hartl D. L. Characterization of bacteriophage P1 library containing inserts of Drosophila DNA of 75-100 kilobase pairs. Chromosoma. 1991 Sep;100(8):487–494. doi: 10.1007/BF00352199. [DOI] [PubMed] [Google Scholar]
  37. Snow R. Recombination in ultraviolet-sensitive strains of Saccharomyces cerevisiae. Mutat Res. 1968 Nov-Dec;6(3):409–418. doi: 10.1016/0027-5107(68)90058-4. [DOI] [PubMed] [Google Scholar]
  38. Stahl F. W. The Holliday junction on its thirtieth anniversary. Genetics. 1994 Oct;138(2):241–246. doi: 10.1093/genetics/138.2.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Stroumbakis N. D., Li Z., Tolias P. P. RNA- and single-stranded DNA-binding (SSB) proteins expressed during Drosophila melanogaster oogenesis: a homolog of bacterial and eukaryotic mitochondrial SSBs. Gene. 1994 Jun 10;143(2):171–177. doi: 10.1016/0378-1119(94)90093-0. [DOI] [PubMed] [Google Scholar]
  40. Szostak J. W., Orr-Weaver T. L., Rothstein R. J., Stahl F. W. The double-strand-break repair model for recombination. Cell. 1983 May;33(1):25–35. doi: 10.1016/0092-8674(83)90331-8. [DOI] [PubMed] [Google Scholar]
  41. Thaler D. S., Stahl M. M., Stahl F. W. Tests of the double-strand-break repair model for red-mediated recombination of phage lambda and plasmid lambda dv. Genetics. 1987 Aug;116(4):501–511. doi: 10.1093/genetics/116.4.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tomkinson A. E., Bardwell A. J., Bardwell L., Tappe N. J., Friedberg E. C. Yeast DNA repair and recombination proteins Rad1 and Rad10 constitute a single-stranded-DNA endonuclease. Nature. 1993 Apr 29;362(6423):860–862. doi: 10.1038/362860a0. [DOI] [PubMed] [Google Scholar]
  43. West S. C. Holliday junctions cleaved by Rad1? Nature. 1995 Jan 5;373(6509):27–28. doi: 10.1038/373027a0. [DOI] [PubMed] [Google Scholar]
  44. White J. H., Lusnak K., Fogel S. Mismatch-specific post-meiotic segregation frequency in yeast suggests a heteroduplex recombination intermediate. Nature. 1985 May 23;315(6017):350–352. doi: 10.1038/315350a0. [DOI] [PubMed] [Google Scholar]
  45. Wilcox D. R., Prakash L. Incision and postincision steps of pyrimidine dimer removal in excision-defective mutants of Saccharomyces cerevisiae. J Bacteriol. 1981 Nov;148(2):618–623. doi: 10.1128/jb.148.2.618-623.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Williamson M. S., Game J. C., Fogel S. Meiotic gene conversion mutants in Saccharomyces cerevisiae. I. Isolation and characterization of pms1-1 and pms1-2. Genetics. 1985 Aug;110(4):609–646. doi: 10.1093/genetics/110.4.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Yamamoto A. H., Brodberg R. K., Banga S. S., Boyd J. B., Mason J. M. Recovery and characterization of hybrid dysgenesis-induced mei-9 and mei-41 alleles of Drosophila melanogaster. Mutat Res. 1990 Mar;229(1):17–28. doi: 10.1016/0027-5107(90)90004-n. [DOI] [PubMed] [Google Scholar]
  48. van Duin M., de Wit J., Odijk H., Westerveld A., Yasui A., Koken M. H., Hoeijmakers J. H., Bootsma D. Molecular characterization of the human excision repair gene ERCC-1: cDNA cloning and amino acid homology with the yeast DNA repair gene RAD10. Cell. 1986 Mar 28;44(6):913–923. doi: 10.1016/0092-8674(86)90014-0. [DOI] [PubMed] [Google Scholar]
  49. van Vuuren A. J., Appeldoorn E., Odijk H., Yasui A., Jaspers N. G., Bootsma D., Hoeijmakers J. H. Evidence for a repair enzyme complex involving ERCC1 and complementing activities of ERCC4, ERCC11 and xeroderma pigmentosum group F. EMBO J. 1993 Sep;12(9):3693–3701. doi: 10.1002/j.1460-2075.1993.tb06044.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES