Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. 1999 Nov; 153(3): 1117–1130.
PMCID: PMC1460819

A novel allele of RAD52 that causes severe DNA repair and recombination deficiencies only in the absence of RAD51 or RAD59.

Abstract

With the use of an intrachromosomal inverted repeat as a recombination reporter, we have shown that mitotic recombination is dependent on the RAD52 gene, but reduced only fivefold by mutation of RAD51. RAD59, a component of the RAD51-independent pathway, was identified previously by screening for mutations that reduced inverted-repeat recombination in a rad51 strain. Here we describe a rad52 mutation, rad52R70K, that also reduced recombination synergistically in a rad51 background. The phenotype of the rad52R70K strain, which includes weak gamma-ray sensitivity, a fourfold reduction in the rate of inverted-repeat recombination, elevated allelic recombination, sporulation proficiency, and a reduction in the efficiency of mating-type switching and single-strand annealing, was similar to that observed for deletion of the RAD59 gene. However, rad52R70K rad59 double mutants showed synergistic defects in ionizing radiation resistance, sporulation, and mating-type switching. These results suggest that Rad52 and Rad59 have partially overlapping functions and that Rad59 can substitute for this function of Rad52 in a RAD51 rad52R70K strain.

Full Text

The Full Text of this article is available as a PDF (227K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Adzuma K, Ogawa T, Ogawa H. Primary structure of the RAD52 gene in Saccharomyces cerevisiae. Mol Cell Biol. 1984 Dec;4(12):2735–2744. [PMC free article] [PubMed]
  • Ajimura M, Leem SH, Ogawa H. Identification of new genes required for meiotic recombination in Saccharomyces cerevisiae. Genetics. 1993 Jan;133(1):51–66. [PMC free article] [PubMed]
  • Bai Y, Symington LS. A Rad52 homolog is required for RAD51-independent mitotic recombination in Saccharomyces cerevisiae. Genes Dev. 1996 Aug 15;10(16):2025–2037. [PubMed]
  • Bendixen C, Sunjevaric I, Bauchwitz R, Rothstein R. Identification of a mouse homologue of the Saccharomyces cerevisiae recombination and repair gene, RAD52. Genomics. 1994 Sep 1;23(1):300–303. [PubMed]
  • Benson FE, Baumann P, West SC. Synergistic actions of Rad51 and Rad52 in recombination and DNA repair. Nature. 1998 Jan 22;391(6665):401–404. [PubMed]
  • Bezzubova OY, Schmidt H, Ostermann K, Heyer WD, Buerstedde JM. Identification of a chicken RAD52 homologue suggests conservation of the RAD52 recombination pathway throughout the evolution of higher eukaryotes. Nucleic Acids Res. 1993 Dec 25;21(25):5945–5949. [PMC free article] [PubMed]
  • Boundy-Mills KL, Livingston DM. A Saccharomyces cerevisiae RAD52 allele expressing a C-terminal truncation protein: activities and intragenic complementation of missense mutations. Genetics. 1993 Jan;133(1):39–49. [PMC free article] [PubMed]
  • Donovan JW, Milne GT, Weaver DT. Homotypic and heterotypic protein associations control Rad51 function in double-strand break repair. Genes Dev. 1994 Nov 1;8(21):2552–2562. [PubMed]
  • Firmenich AA, Elias-Arnanz M, Berg P. A novel allele of Saccharomyces cerevisiae RFA1 that is deficient in recombination and repair and suppressible by RAD52. Mol Cell Biol. 1995 Mar;15(3):1620–1631. [PMC free article] [PubMed]
  • Nguyen MM, Livingston DM. Cold-sensitive rad52 alleles of yeast. Curr Genet. 1997 Aug;32(2):100–107. [PubMed]
  • Game JC, Mortimer RK. A genetic study of x-ray sensitive mutants in yeast. Mutat Res. 1974 Sep;24(3):281–292. [PubMed]
  • Nickoloff JA, Chen EY, Heffron F. A 24-base-pair DNA sequence from the MAT locus stimulates intergenic recombination in yeast. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7831–7835. [PMC free article] [PubMed]
  • Game JC, Zamb TJ, Braun RJ, Resnick M, Roth RM. The Role of Radiation (rad) Genes in Meiotic Recombination in Yeast. Genetics. 1980 Jan;94(1):51–68. [PMC free article] [PubMed]
  • Ogawa T, Shinohara A, Nabetani A, Ikeya T, Yu X, Egelman EH, Ogawa H. RecA-like recombination proteins in eukaryotes: functions and structures of RAD51 genes. Cold Spring Harb Symp Quant Biol. 1993;58:567–576. [PubMed]
  • Hays SL, Firmenich AA, Berg P. Complex formation in yeast double-strand break repair: participation of Rad51, Rad52, Rad55, and Rad57 proteins. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):6925–6929. [PMC free article] [PubMed]
  • Ozenberger BA, Roeder GS. A unique pathway of double-strand break repair operates in tandemly repeated genes. Mol Cell Biol. 1991 Mar;11(3):1222–1231. [PMC free article] [PubMed]
  • Park MS, Ludwig DL, Stigger E, Lee SH. Physical interaction between human RAD52 and RPA is required for homologous recombination in mammalian cells. J Biol Chem. 1996 Aug 2;271(31):18996–19000. [PubMed]
  • Ho KS. The gene dosage effect of the rad52 mutation on X-ray survival curves of tetraploid yeast strains. Mutat Res. 1975 Dec;33(2-3):165–172. [PubMed]
  • Prado F, Aguilera A. Role of reciprocal exchange, one-ended invasion crossover and single-strand annealing on inverted and direct repeat recombination in yeast: different requirements for the RAD1, RAD10, and RAD52 genes. Genetics. 1995 Jan;139(1):109–123. [PMC free article] [PubMed]
  • Prakash S, Prakash L, Burke W, Montelone BA. Effects of the RAD52 Gene on Recombination in SACCHAROMYCES CEREVISIAE. Genetics. 1980 Jan;94(1):31–50. [PMC free article] [PubMed]
  • Rattray AJ, Symington LS. Use of a chromosomal inverted repeat to demonstrate that the RAD51 and RAD52 genes of Saccharomyces cerevisiae have different roles in mitotic recombination. Genetics. 1994 Nov;138(3):587–595. [PMC free article] [PubMed]
  • Ivanov EL, Sugawara N, Fishman-Lobell J, Haber JE. Genetic requirements for the single-strand annealing pathway of double-strand break repair in Saccharomyces cerevisiae. Genetics. 1996 Mar;142(3):693–704. [PMC free article] [PubMed]
  • Rattray AJ, Symington LS. Multiple pathways for homologous recombination in Saccharomyces cerevisiae. Genetics. 1995 Jan;139(1):45–56. [PMC free article] [PubMed]
  • Kaytor MD, Livingston DM. Saccharomyces cerevisiae RAD52 alleles temperature-sensitive for the repair of DNA double-strand breaks. Genetics. 1994 Aug;137(4):933–944. [PMC free article] [PubMed]
  • Resnick MA, Martin P. The repair of double-strand breaks in the nuclear DNA of Saccharomyces cerevisiae and its genetic control. Mol Gen Genet. 1976 Jan 16;143(2):119–129. [PubMed]
  • Kaytor MD, Livingston DM. Allele-specific suppression of temperature-sensitive mutations of the Saccharomyces cerevisiae RAD52 gene. Curr Genet. 1996 Feb;29(3):203–210. [PubMed]
  • Resnick MA, Nitiss J, Edwards C, Malone RE. Meiosis can induce recombination in rad52 mutants of Saccharomyces cerevisiae. Genetics. 1986 Jul;113(3):531–550. [PMC free article] [PubMed]
  • Kaytor MD, Nguyen M, Livingston DM. The complexity of the interaction between RAD52 and SRS2. Genetics. 1995 Aug;140(4):1441–1442. [PMC free article] [PubMed]
  • Rijkers T, Van Den Ouweland J, Morolli B, Rolink AG, Baarends WM, Van Sloun PP, Lohman PH, Pastink A. Targeted inactivation of mouse RAD52 reduces homologous recombination but not resistance to ionizing radiation. Mol Cell Biol. 1998 Nov;18(11):6423–6429. [PMC free article] [PubMed]
  • Klein HL. RDH54, a RAD54 homologue in Saccharomyces cerevisiae, is required for mitotic diploid-specific recombination and repair and for meiosis. Genetics. 1997 Dec;147(4):1533–1543. [PMC free article] [PubMed]
  • Schild D. Suppression of a new allele of the yeast RAD52 gene by overexpression of RAD51, mutations in srs2 and ccr4, or mating-type heterozygosity. Genetics. 1995 May;140(1):115–127. [PMC free article] [PubMed]
  • Malkova A, Ivanov EL, Haber JE. Double-strand break repair in the absence of RAD51 in yeast: a possible role for break-induced DNA replication. Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7131–7136. [PMC free article] [PubMed]
  • Schwacha A, Kleckner N. Interhomolog bias during meiotic recombination: meiotic functions promote a highly differentiated interhomolog-only pathway. Cell. 1997 Sep 19;90(6):1123–1135. [PubMed]
  • Malone RE, Montelone BA, Edwards C, Carney K, Hoekstra MF. A reexamination of the role of the RAD52 gene in spontaneous mitotic recombination. Curr Genet. 1988 Sep;14(3):211–223. [PubMed]
  • Shinohara A, Ogawa T. Stimulation by Rad52 of yeast Rad51-mediated recombination. Nature. 1998 Jan 22;391(6665):404–407. [PubMed]
  • Milne GT, Weaver DT. Dominant negative alleles of RAD52 reveal a DNA repair/recombination complex including Rad51 and Rad52. Genes Dev. 1993 Sep;7(9):1755–1765. [PubMed]
  • Shinohara A, Gasior S, Ogawa T, Kleckner N, Bishop DK. Saccharomyces cerevisiae recA homologues RAD51 and DMC1 have both distinct and overlapping roles in meiotic recombination. Genes Cells. 1997 Oct;2(10):615–629. [PubMed]
  • Mortensen UH, Bendixen C, Sunjevaric I, Rothstein R. DNA strand annealing is promoted by the yeast Rad52 protein. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10729–10734. [PMC free article] [PubMed]
  • Shinohara M, Shita-Yamaguchi E, Buerstedde JM, Shinagawa H, Ogawa H, Shinohara A. Characterization of the roles of the Saccharomyces cerevisiae RAD54 gene and a homologue of RAD54, RDH54/TID1, in mitosis and meiosis. Genetics. 1997 Dec;147(4):1545–1556. [PMC free article] [PubMed]
  • Mortimer RK, Contopoulou R, Schild D. Mitotic chromosome loss in a radiation-sensitive strain of the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5778–5782. [PMC free article] [PubMed]
  • Shinohara A, Shinohara M, Ohta T, Matsuda S, Ogawa T. Rad52 forms ring structures and co-operates with RPA in single-strand DNA annealing. Genes Cells. 1998 Mar;3(3):145–156. [PubMed]
  • Sung P, Robberson DL. DNA strand exchange mediated by a RAD51-ssDNA nucleoprotein filament with polarity opposite to that of RecA. Cell. 1995 Aug 11;82(3):453–461. [PubMed]
  • Symington LS. Homologous recombination is required for the viability of rad27 mutants. Nucleic Acids Res. 1998 Dec 15;26(24):5589–5595. [PMC free article] [PubMed]
  • Smith J, Rothstein R. An allele of RFA1 suppresses RAD52-dependent double-strand break repair in Saccharomyces cerevisiae. Genetics. 1999 Feb;151(2):447–458. [PMC free article] [PubMed]
  • Sugawara N, Haber JE. Characterization of double-strand break-induced recombination: homology requirements and single-stranded DNA formation. Mol Cell Biol. 1992 Feb;12(2):563–575. [PMC free article] [PubMed]
  • White CI, Haber JE. Intermediates of recombination during mating type switching in Saccharomyces cerevisiae. EMBO J. 1990 Mar;9(3):663–673. [PMC free article] [PubMed]
  • Sugawara N, Ivanov EL, Fishman-Lobell J, Ray BL, Wu X, Haber JE. DNA structure-dependent requirements for yeast RAD genes in gene conversion. Nature. 1995 Jan 5;373(6509):84–86. [PubMed]
  • Willis KK, Klein HL. Intrachromosomal recombination in Saccharomyces cerevisiae: reciprocal exchange in an inverted repeat and associated gene conversion. Genetics. 1987 Dec;117(4):633–643. [PMC free article] [PubMed]
  • Yamaguchi-Iwai Y, Sonoda E, Buerstedde JM, Bezzubova O, Morrison C, Takata M, Shinohara A, Takeda S. Homologous recombination, but not DNA repair, is reduced in vertebrate cells deficient in RAD52. Mol Cell Biol. 1998 Nov;18(11):6430–6435. [PMC free article] [PubMed]
  • Sung P. Catalysis of ATP-dependent homologous DNA pairing and strand exchange by yeast RAD51 protein. Science. 1994 Aug 26;265(5176):1241–1243. [PubMed]
  • Zou H, Rothstein R. Holliday junctions accumulate in replication mutants via a RecA homolog-independent mechanism. Cell. 1997 Jul 11;90(1):87–96. [PubMed]
  • Sung P. Function of yeast Rad52 protein as a mediator between replication protein A and the Rad51 recombinase. J Biol Chem. 1997 Nov 7;272(45):28194–28197. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...