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Gene Review

RAD52  -  recombinase RAD52

Saccharomyces cerevisiae S288c

Synonyms: DNA repair and recombination protein RAD52, YML032C
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Disease relevance of RAD52


High impact information on RAD52

  • Finally, components of the INO80 complex show synthetic genetic interactions with the RAD52 DNA repair pathway, the main pathway for DSB repair in yeast [5].
  • At one locus, chromosomes with terminal deletions gained a new telomere through a Rad52p-dependent, Rad51p-independent process consistent with break-induced replication [6].
  • Mutations in RAD27 cause increased rates of mitotic crossing over and are lethal in combination with mutations in RAD51 and RAD52 [7].
  • Its biological importance is underscored by the conservation of many RAD52 pathway genes, including RAD54, from fungi to humans [8].
  • We have constructed a new generation yeast artificial chromosome (YAC) library from female C57BL/10 mice in a recombination-deficient strain of Saccharomyces cerevisiae carrying a mutation in the RAD52 gene [9].

Biological context of RAD52

  • We find, however, that only RAD52 is required when the donor sequence is simultaneously not silenced and located on a plasmid [10].
  • In the yeast Saccharomyces cerevisiae, mutations in the genes RAD51 or RAD52 result in severe defects in genetic recombination and the repair of double-strand DNA breaks [11].
  • Overexpression of RAD52 was found to suppress the DNA repair and recombination defects conferred by the rad59 mutation, suggesting that these proteins have overlapping roles or function as a complex [12].
  • Both proteins are also important members of the RAD52 group which controls recombinational DNA damage repair of double-strand breaks and other DNA lesions in Saccharomyces cerevisiae [13].
  • Previously, we have shown that in the absence of RAD52, repair is nearly absent and diploid cells lose the broken chromosome; however, in cells lacking RAD51, gene conversion is absent but cells can repair the DSB by BIR [14].

Anatomical context of RAD52


Associations of RAD52 with chemical compounds

  • In this study, we found that SGS1 forms part of the RAD52 epistasis group when cells are exposed to MMS [19].
  • These results, taken together with the recombinogenic effects of Cr(VI) in yeast containing a functional RAD52 gene, suggest that RAD52-mediated recombination is critical for the normal processing of lethal Cr-induced genetic lesions and exit from G(2) arrest [20].
  • In addition, we provide evidence for the activation of the RAD52 recombinational pathway in the pol30-119 mutant and we infer that SUMO conjugation at the lysine 164 residue of PCNA has a role in suppressing the Rad52-dependent postreplicational repair pathway [21].
  • A rad52 mutant was more sensitive to cisplatin than the RAD52 parental strain, which reveals that Rad52, a double-strand break repair protein, repairs cisplatin-DNA adducts, probably interstrand cross-links [22].
  • However, the rad6 and rad52 mutants show a normal dose-dependent increase in DDRA2 transcript levels after NQO or MNNG exposure [23].

Physical interactions of RAD52

  • Yeast Rad52 protein interacts with Rad51 protein, binds single-stranded DNA and stimulates annealing of complementary single-stranded DNA [24].
  • The yeast recombinational repair protein Rad59 interacts with Rad52 and stimulates single-strand annealing [25].
  • We show that the Saccharomyces cerevisiae recombination protein Rad52 and the single-strand DNA-binding protein RPA assemble into cytologically detectable subnuclear complexes (foci) during meiotic recombination [26].
  • Surprisingly, these heterogeneous arrays of Rap1p binding sites generate telomeres through a RAD52-dependent fusion resolution reaction that results in an inversion of the original array [27].
  • Complementation tests using heterozygous diploid strains showed that the pso4 protein might interact with the rad52 protein during repair of 8-mop photolesions [28].
  • The nucleolar exclusion of Rad52 recombination foci entails Mre11 and Smc5-Smc6 complexes and depends on Rad52 SUMO (small ubiquitin-related modifier) modification [29].

Co-localisations of RAD52


Regulatory relationships of RAD52

  • Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A [24].
  • Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae [19].
  • This inability of srs2 to suppress rad6 is irrespective of the incubation temperature or whether pup1 is suppressing the temperature-sensitive rad52 mutation [31].
  • An allele of RFA1 suppresses RAD52-dependent double-strand break repair in Saccharomyces cerevisiae [32].
  • The nuclease RhoNuc (previously designated yNucR), encoded by the RNC1 (previously designated NUC2) gene and regulated by the RAD52 gene, is not required for recombination when one substrate is single-stranded but is essential for the majority of recombination events when both substrates are double-stranded [33].

Other interactions of RAD52

  • The DNA-binding properties of hRad52 indicate that Rad52 is involved in an early stage of Rad51-mediated recombination [11].
  • The repair of DNA double-strand breaks in Saccharomyces cerevisiae requires genes of the RAD52 epistasis group, of which RAD55 and RAD57 are members [34].
  • In Saccharomyces cerevisiae, RAD1 and RAD52 are required for alternate pathways of mitotic recombination [35].
  • Deletion of both RAD50 and RAD51 produces a phenotype similar to that produced by deletion of RAD52 [36].
  • A mutant with a deletion of RAD59, a homologue of RAD52, was defective for SSA, especially when the homologous-sequence length was short; however, even with 1.17-kb substrates, SSA was reduced fourfold [37].
  • We surmise that both of these pathways operate in a nonrecombinational manner, Rad5 by mediating replication fork regression and template switching via its DNA helicase activity and Rad52 via a synthesis-dependent strand annealing mode [38].
  • This regulation of Rad52-mediated annealing suggests a control function for Rad51 in deciding the recombination path taken for a processed DNA break; the ssDNA can be directed to either Rad51-mediated DNA strand invasion or to Rad52-mediated DNA annealing [39].

Analytical, diagnostic and therapeutic context of RAD52

  • Can(r) mutation spectrum analysis of pol32Delta strains revealed a substantial increase in the frequency of deletions and duplications (primarily deletions) of sequences flanked by short direct repeats, which appears to be RAD52 and RAD10 independent [40].
  • Translocations occurred in the RAD52+ genetic background and were characterized by orthogonal field alternating gel electrophoresis of yeast chromosomal DNA and by standard genetic techniques [41].
  • First, flow cytometric measurements of DNA content and immunofluorescence were used to determine the phase-specific levels of RAD51 and RAD52 protein expression in irradiated and control populations [42].
  • Here we demonstrate physical interaction between Rad52 and Rad59 using the yeast two-hybrid system and co-immunoprecipitation from yeast extracts [25].
  • An analysis by pulsed-field gel electrophoresis and epistasis analyses indicated that Sgs1 is required for DSB repair that involves Rad52 [43].


  1. Induction of mitotic crossing-over by the topoisomerase II poison DACA (N-[2-dimethylamino)ethyl]acridine-4-carboxamide) in Saccharomyces cerevisiae. Ferguson, L.R., Turner, P.M., Baguley, B.C. Mutat. Res. (1993) [Pubmed]
  2. Yeast gene RAD52 can substitute for phage T4 gene 46 or 47 in carrying out recombination and DNA repair. Chen, D.S., Bernstein, H. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  3. Rad52 partially substitutes for the Rad51 paralog XRCC3 in maintaining chromosomal integrity in vertebrate cells. Fujimori, A., Tachiiri, S., Sonoda, E., Thompson, L.H., Dhar, P.K., Hiraoka, M., Takeda, S., Zhang, Y., Reth, M., Takata, M. EMBO J. (2001) [Pubmed]
  4. The human Rad52 protein exists as a heptameric ring. Stasiak, A.Z., Larquet, E., Stasiak, A., Müller, S., Engel, A., Van Dyck, E., West, S.C., Egelman, E.H. Curr. Biol. (2000) [Pubmed]
  5. INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Morrison, A.J., Highland, J., Krogan, N.J., Arbel-Eden, A., Greenblatt, J.F., Haber, J.E., Shen, X. Cell (2004) [Pubmed]
  6. Telomere dysfunction increases mutation rate and genomic instability. Hackett, J.A., Feldser, D.M., Greider, C.W. Cell (2001) [Pubmed]
  7. A novel mutation avoidance mechanism dependent on S. cerevisiae RAD27 is distinct from DNA mismatch repair. Tishkoff, D.X., Filosi, N., Gaida, G.M., Kolodner, R.D. Cell (1997) [Pubmed]
  8. Disruption of mouse RAD54 reduces ionizing radiation resistance and homologous recombination. Essers, J., Hendriks, R.W., Swagemakers, S.M., Troelstra, C., de Wit, J., Bootsma, D., Hoeijmakers, J.H., Kanaar, R. Cell (1997) [Pubmed]
  9. Construction of a mouse yeast artificial chromosome library in a recombination-deficient strain of yeast. Chartier, F.L., Keer, J.T., Sutcliffe, M.J., Henriques, D.A., Mileham, P., Brown, S.D. Nat. Genet. (1992) [Pubmed]
  10. DNA structure-dependent requirements for yeast RAD genes in gene conversion. Sugawara, N., Ivanov, E.L., Fishman-Lobell, J., Ray, B.L., Wu, X., Haber, J.E. Nature (1995) [Pubmed]
  11. Synergistic actions of Rad51 and Rad52 in recombination and DNA repair. Benson, F.E., Baumann, P., West, S.C. Nature (1998) [Pubmed]
  12. A Rad52 homolog is required for RAD51-independent mitotic recombination in Saccharomyces cerevisiae. Bai, Y., Symington, L.S. Genes Dev. (1996) [Pubmed]
  13. Recombinational repair in yeast: functional interactions between Rad51 and Rad54 proteins. Clever, B., Interthal, H., Schmuckli-Maurer, J., King, J., Sigrist, M., Heyer, W.D. EMBO J. (1997) [Pubmed]
  14. Genetic requirements for RAD51- and RAD54-independent break-induced replication repair of a chromosomal double-strand break. Signon, L., Malkova, A., Naylor, M.L., Klein, H., Haber, J.E. Mol. Cell. Biol. (2001) [Pubmed]
  15. MMS1 protects against replication-dependent DNA damage in Saccharomyces cerevisiae. Hryciw, T., Tang, M., Fontanie, T., Xiao, W. Mol. Genet. Genomics (2002) [Pubmed]
  16. Yeast cell-free system that catalyses joint-molecule formation in a Rad51p- and Rad52p-dependent fashion. Nagaraj, V., Norris, D. Biochem. J. (2000) [Pubmed]
  17. Homologous recombination, but not DNA repair, is reduced in vertebrate cells deficient in RAD52. Yamaguchi-Iwai, Y., Sonoda, E., Buerstedde, J.M., Bezzubova, O., Morrison, C., Takata, M., Shinohara, A., Takeda, S. Mol. Cell. Biol. (1998) [Pubmed]
  18. The human and mouse homologs of the yeast RAD52 gene: cDNA cloning, sequence analysis, assignment to human chromosome 12p12.2-p13, and mRNA expression in mouse tissues. Shen, Z., Denison, K., Lobb, R., Gatewood, J.M., Chen, D.J. Genomics (1995) [Pubmed]
  19. Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae. Onoda, F., Seki, M., Miyajima, A., Enomoto, T. Mol. Gen. Genet. (2001) [Pubmed]
  20. Effects of hexavalent chromium on the survival and cell cycle distribution of DNA repair-deficient S. cerevisiae. O'Brien, T.J., Fornsaglio, J.L., Ceryak, S., Patierno, S.R. DNA Repair (Amst.) (2002) [Pubmed]
  21. Opposing effects of ubiquitin conjugation and SUMO modification of PCNA on replicational bypass of DNA lesions in Saccharomyces cerevisiae. Haracska, L., Torres-Ramos, C.A., Johnson, R.E., Prakash, S., Prakash, L. Mol. Cell. Biol. (2004) [Pubmed]
  22. The HMG-domain protein Ixr1 blocks excision repair of cisplatin-DNA adducts in yeast. McA'Nulty, M.M., Lippard, S.J. Mutat. Res. (1996) [Pubmed]
  23. Transcriptional regulation of DNA damage responsive (DDR) genes in different rad mutant strains of Saccharomyces cerevisiae. Maga, J.A., McClanahan, T.A., McEntee, K. Mol. Gen. Genet. (1986) [Pubmed]
  24. Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A. New, J.H., Sugiyama, T., Zaitseva, E., Kowalczykowski, S.C. Nature (1998) [Pubmed]
  25. The yeast recombinational repair protein Rad59 interacts with Rad52 and stimulates single-strand annealing. Davis, A.P., Symington, L.S. Genetics (2001) [Pubmed]
  26. Rad52 associates with RPA and functions with rad55 and rad57 to assemble meiotic recombination complexes. Gasior, S.L., Wong, A.K., Kora, Y., Shinohara, A., Bishop, D.K. Genes Dev. (1998) [Pubmed]
  27. Telomere formation by rap1p binding site arrays reveals end-specific length regulation requirements and active telomeric recombination. Grossi, S., Bianchi, A., Damay, P., Shore, D. Mol. Cell. Biol. (2001) [Pubmed]
  28. Further characterization of the yeast pso4-1 mutant: interaction with rad51 and rad52 mutants after photoinduced psoralen lesions. de Morais, M.A., Vicente, E.J., Brozmanova, J., Schenberg, A.C., Henriques, J.A. Curr. Genet. (1996) [Pubmed]
  29. The Smc5-Smc6 complex and SUMO modification of Rad52 regulates recombinational repair at the ribosomal gene locus. Torres-Rosell, J., Sunjevaric, I., De Piccoli, G., Sacher, M., Eckert-Boulet, N., Reid, R., Jentsch, S., Rothstein, R., Aragón, L., Lisby, M. Nat. Cell Biol. (2007) [Pubmed]
  30. Localization and dynamic relocalization of mammalian Rad52 during the cell cycle and in response to DNA damage. Liu, Y., Li, M., Lee, E.Y., Maizels, N. Curr. Biol. (1999) [Pubmed]
  31. The effect of a suppressed rad52 mutation on the suppression of rad6 by srs2. Nguyen, M.M., Livingston, D.M. Yeast (1997) [Pubmed]
  32. An allele of RFA1 suppresses RAD52-dependent double-strand break repair in Saccharomyces cerevisiae. Smith, J., Rothstein, R. Genetics (1999) [Pubmed]
  33. In-vitro recombination in rad and rnc mutants of Saccharomyces cerevisiae. Moore, P.D., Simon, J.R., Wallace, L.J., Chow, T.Y. Curr. Genet. (1993) [Pubmed]
  34. Complex formation in yeast double-strand break repair: participation of Rad51, Rad52, Rad55, and Rad57 proteins. Hays, S.L., Firmenich, A.A., Berg, P. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  35. Rsp5, a ubiquitin-protein ligase, is involved in degradation of the single-stranded-DNA binding protein rfa1 in Saccharomyces cerevisiae. Erdeniz, N., Rothstein, R. Mol. Cell. Biol. (2000) [Pubmed]
  36. Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events. Chen, Q., Ijpma, A., Greider, C.W. Mol. Cell. Biol. (2001) [Pubmed]
  37. DNA length dependence of the single-strand annealing pathway and the role of Saccharomyces cerevisiae RAD59 in double-strand break repair. Sugawara, N., Ira, G., Haber, J.E. Mol. Cell. Biol. (2000) [Pubmed]
  38. Requirement of RAD52 group genes for postreplication repair of UV-damaged DNA in Saccharomyces cerevisiae. Gangavarapu, V., Prakash, S., Prakash, L. Mol. Cell. Biol. (2007) [Pubmed]
  39. Rad51 protein controls Rad52-mediated DNA annealing. Wu, Y., Kantake, N., Sugiyama, T., Kowalczykowski, S.C. J. Biol. Chem. (2008) [Pubmed]
  40. Pol32, a subunit of Saccharomyces cerevisiae DNA polymerase delta, suppresses genomic deletions and is involved in the mutagenic bypass pathway. Huang, M.E., Rio, A.G., Galibert, M.D., Galibert, F. Genetics (2002) [Pubmed]
  41. Direction of chromosome rearrangements in Saccharomyces cerevisiae by use of his3 recombinational substrates. Fasullo, M.T., Davis, R.W. Mol. Cell. Biol. (1988) [Pubmed]
  42. Cell cycle-dependent protein expression of mammalian homologs of yeast DNA double-strand break repair genes Rad51 and Rad52. Chen, F., Nastasi, A., Shen, Z., Brenneman, M., Crissman, H., Chen, D.J. Mutat. Res. (1997) [Pubmed]
  43. The ability of Sgs1 to interact with DNA topoisomerase III is essential for damage-induced recombination. Ui, A., Seki, M., Ogiwara, H., Onodera, R., Fukushige, S., Onoda, F., Enomoto, T. DNA Repair (Amst.) (2005) [Pubmed]
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