rad52 dna repair and recombination protein


Summary: A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.

Top Publications

  1. Park M. Expression of human RAD52 confers resistance to ionizing radiation in mammalian cells. J Biol Chem. 1995;270:15467-70 pubmed
    ..These observations suggest that homologous recombination mediated by RAD52 is involved in double-stranded break repair in mammalian cells. ..
  2. Navadgi V, Shukla A, Rao B. Effect of DNA sequence and nucleotide cofactors on hRad51 binding to ssDNA: role of hRad52 in recruitment. Biochem Biophys Res Commun. 2005;334:696-701 pubmed
    ..These results help us to model important mechanistic steps of hRad51 presynapsis on ssDNA templates. ..
  3. Sacher M, Pfander B, Hoege C, Jentsch S. Control of Rad52 recombination activity by double-strand break-induced SUMO modification. Nat Cell Biol. 2006;8:1284-90 pubmed
    ..Furthermore, our data indicate that sumoylation becomes particularly relevant for those Rad52 molecules that are engaged in recombination. ..
  4. Plate I, Albertsen L, Lisby M, Hallwyl S, Feng Q, Seong C, et al. Rad52 multimerization is important for its nuclear localization in Saccharomyces cerevisiae. DNA Repair (Amst). 2008;7:57-66 pubmed
    ..Based on the results we propose a model where the additive effect of multiple NLS(Rad52) sequences in a Rad52 ring-structure ensures efficient nuclear localization of Rad52. ..
  5. Seong C, Sehorn M, Plate I, Shi I, Song B, Chi P, et al. Molecular anatomy of the recombination mediator function of Saccharomyces cerevisiae Rad52. J Biol Chem. 2008;283:12166-74 pubmed publisher
    ..Our results provide a mechanistic framework for rationalizing the multi-faceted role of Rad52 in recombination and DNA repair. ..
  6. Shinohara A, Ogawa T. Stimulation by Rad52 of yeast Rad51-mediated recombination. Nature. 1998;391:404-7 pubmed
    ..We conclude that this binding is crucial in recombination and that it facilitates the formation of Rad51 nucleoprotein filaments. ..
  7. Krejci L, Damborsky J, Thomsen B, Duno M, Bendixen C. Molecular dissection of interactions between Rad51 and members of the recombination-repair group. Mol Cell Biol. 2001;21:966-76 pubmed
  8. Milne G, Ho T, Weaver D. Modulation of Saccharomyces cerevisiae DNA double-strand break repair by SRS2 and RAD51. Genetics. 1995;139:1189-99 pubmed
    ..Thus, RAD52-dependent recombinational repair is controlled both negatively and positively. ..
  9. Feng Q, Düring L, de Mayolo A, Lettier G, Lisby M, Erdeniz N, et al. Rad52 and Rad59 exhibit both overlapping and distinct functions. DNA Repair (Amst). 2007;6:27-37 pubmed
    ..Importantly, the N-terminus of Rad52 possesses functions not supplied by Rad59, which may account for its central role in homologous recombination. ..

More Information


  1. Yoshida J, Umezu K, Maki H. Positive and negative roles of homologous recombination in the maintenance of genome stability in Saccharomyces cerevisiae. Genetics. 2003;164:31-46 pubmed
    ..In contrast, other recombination pathways can occur at a substantial level even in the absence of one of the genes and contribute to generating various chromosome rearrangements. ..
  2. Kagawa W, Kurumizaka H, Ishitani R, Fukai S, Nureki O, Shibata T, et al. Crystal structure of the homologous-pairing domain from the human Rad52 recombinase in the undecameric form. Mol Cell. 2002;10:359-71 pubmed
    ..A mutational analysis revealed that the amino acid residues located between the beta-beta-beta-alpha fold and the characteristic hairpin loop are essential for ssDNA and dsDNA binding. ..
  3. New J, Kowalczykowski S. Rad52 protein has a second stimulatory role in DNA strand exchange that complements replication protein-A function. J Biol Chem. 2002;277:26171-6 pubmed
    ..We propose that Rad52 protein acts by stabilizing the Rad51 presynaptic filament. ..
  4. Seong C, Colavito S, Kwon Y, Sung P, Krejci L. Regulation of Rad51 recombinase presynaptic filament assembly via interactions with the Rad52 mediator and the Srs2 anti-recombinase. J Biol Chem. 2009;284:24363-71 pubmed publisher
    ..Moreover, our biochemical studies have helped identify A320V as a separation-of-function mutation in Rad51 with regards to a differential ablation of Rad52 interaction. ..
  5. Xiao W, Chow B, Rathgeber L. The repair of DNA methylation damage in Saccharomyces cerevisiae. Curr Genet. 1996;30:461-8 pubmed
    ..Based on the above analyses, we discuss possible mechanisms for the repair of methylation damage by various pathways. ..
  6. Rijkers T, van den Ouweland J, Morolli B, Rolink A, Baarends W, Van Sloun P, et al. Targeted inactivation of mouse RAD52 reduces homologous recombination but not resistance to ionizing radiation. Mol Cell Biol. 1998;18:6423-9 pubmed
    ..The effect of inactivating MmRAD52 suggests the presence of genes functionally related to MmRAD52, which can partly compensate for the absence of MmRad52 protein. ..
  7. Burgess R, Rahman S, Lisby M, Rothstein R, Zhao X. The Slx5-Slx8 complex affects sumoylation of DNA repair proteins and negatively regulates recombination. Mol Cell Biol. 2007;27:6153-62 pubmed
    ..In addition, the complex inhibits Rad51-independent recombination via modulating the sumoylation of DNA repair proteins. ..
  8. Wolner B, Van Komen S, Sung P, Peterson C. Recruitment of the recombinational repair machinery to a DNA double-strand break in yeast. Mol Cell. 2003;12:221-32 pubmed
    ..These studies provide a near comprehensive view of the molecular events required for the in vivo assembly of a functional Rad51p presynaptic filament. ..
  9. Irmisch A, Ampatzidou E, Mizuno K, O Connell M, Murray J. Smc5/6 maintains stalled replication forks in a recombination-competent conformation. EMBO J. 2009;28:144-55 pubmed publisher
    ..We propose that Smc5/6 is required to maintain stalled forks in a stable recombination-competent conformation primed for replication restart. ..
  10. Singleton M, Wentzell L, Liu Y, West S, Wigley D. Structure of the single-strand annealing domain of human RAD52 protein. Proc Natl Acad Sci U S A. 2002;99:13492-7 pubmed
    ..A large, positively charged groove runs along the surface of the ring, readily suggesting a mechanism by which RAD52 presents the single strand for reannealing with complementary single-stranded DNA. ..
  11. Nimonkar A, Sica R, Kowalczykowski S. Rad52 promotes second-end DNA capture in double-stranded break repair to form complement-stabilized joint molecules. Proc Natl Acad Sci U S A. 2009;106:3077-82 pubmed publisher
    ..These studies support a role for Rad52-promoted annealing in the formation of Holliday junctions in DSB repair. ..
  12. Barlow J, Rothstein R. Rad52 recruitment is DNA replication independent and regulated by Cdc28 and the Mec1 kinase. EMBO J. 2009;28:1121-30 pubmed publisher
    ..We propose that B-type cyclins promote the recruitment of Rad52 to sites of DNA damage, whereas Mec1 inhibits spurious recombination at stalled replication forks. ..
  13. Sugiyama T, Kowalczykowski S. Rad52 protein associates with replication protein A (RPA)-single-stranded DNA to accelerate Rad51-mediated displacement of RPA and presynaptic complex formation. J Biol Chem. 2002;277:31663-72 pubmed
    ..This acceleration probably involves direct interactions with both Rad51 protein and RPA. Detection of a Rad52-RPA-ssDNA co-complex suggests that this co-complex is an intermediate in the displacement process. ..
  14. Van Dyck E, Stasiak A, Stasiak A, West S. Visualization of recombination intermediates produced by RAD52-mediated single-strand annealing. EMBO Rep. 2001;2:905-9 pubmed
  15. Morrison A, Highland J, Krogan N, Arbel Eden A, Greenblatt J, Haber J, et al. INO80 and gamma-H2AX interaction links ATP-dependent chromatin remodeling to DNA damage repair. Cell. 2004;119:767-75 pubmed
    ..Our findings reveal a new role of ATP-dependent chromatin remodeling in nuclear processes and suggest that an ATP-dependent chromatin remodeling complex can read a DNA repair histone code. ..
  16. Andaluz E, Bellido A, Gomez Raja J, Selmecki A, Bouchonville K, Calderone R, et al. Rad52 function prevents chromosome loss and truncation in Candida albicans. Mol Microbiol. 2011;79:1462-82 pubmed publisher
    ..CIN of GLH isolates is reminiscent of genomic alterations leading to cancer in human cells, and support the mutator hypothesis in which a mutator mutation or CIN phenotype facilitate more mutations/aneuploidies. ..
  17. Wu Y, Siino J, Sugiyama T, Kowalczykowski S. The DNA binding preference of RAD52 and RAD59 proteins: implications for RAD52 and RAD59 protein function in homologous recombination. J Biol Chem. 2006;281:40001-9 pubmed
    ..cerevisiae Rad52 and Rad59 proteins and their eukaryotic counterparts function by binding to single-stranded DNA formed as intermediates of recombination rather than by binding to the unprocessed DNA double-strand break. ..
  18. Cortes Ledesma F, Malagon F, Aguilera A. A novel yeast mutation, rad52-L89F, causes a specific defect in Rad51-independent recombination that correlates with a reduced ability of Rad52-L89F to interact with Rad59. Genetics. 2004;168:553-7 pubmed
    ..These results support the idea that Rad59 acts in homologous recombination via physical interaction with Rad52. ..
  19. Sugiyama T, Kantake N, Wu Y, Kowalczykowski S. Rad52-mediated DNA annealing after Rad51-mediated DNA strand exchange promotes second ssDNA capture. EMBO J. 2006;25:5539-48 pubmed
    ..We also demonstrate that the two activities of Rad52, recruiting Rad51 and annealing DNA, are coordinated in DNA strand exchange and second ssDNA capture. ..
  20. Motycka T, Bessho T, Post S, Sung P, Tomkinson A. Physical and functional interaction between the XPF/ERCC1 endonuclease and hRad52. J Biol Chem. 2004;279:13634-9 pubmed
    ..We propose that the ternary complex of hRad52 and XPF/ERCC1 is the active species that processes recombination intermediates generated during the repair of DNA double strand breaks and in homology-dependent gene targeting events. ..
  21. Khadaroo B, Teixeira M, Luciano P, Eckert Boulet N, Germann S, Simon M, et al. The DNA damage response at eroded telomeres and tethering to the nuclear pore complex. Nat Cell Biol. 2009;11:980-7 pubmed publisher
    ..Our results link the DNA damage response at eroded telomeres to changes in subnuclear localization and suggest the existence of collapsed replication forks at eroded telomeres. ..
  22. Schär P, Herrmann G, Daly G, Lindahl T. A newly identified DNA ligase of Saccharomyces cerevisiae involved in RAD52-independent repair of DNA double-strand breaks. Genes Dev. 1997;11:1912-24 pubmed
    ..The mutant phenotypes are consistent with functions of LIG4 in an illegitimate DNA end-joining pathway and ensuring efficient meiosis. ..
  23. Shinohara M, Shita Yamaguchi E, Buerstedde J, 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;147:1545-56 pubmed
    ..These results suggest that one of the differences between the late stages of mitotic recombination and meiotic recombination might be specified by differential dependency on the Rad54 and Rdh54/Tid1 proteins. ..
  24. Yáñez R, Porter A. Differential effects of Rad52p overexpression on gene targeting and extrachromosomal homologous recombination in a human cell line. Nucleic Acids Res. 2002;30:740-8 pubmed
    ..The data also argue against Rad52p overexpression as a means of promoting gene targeting, and highlight the limitations of using a single HR assay to assess the overall status of HR. ..
  25. Grandin N, Damon C, Charbonneau M. Cdc13 prevents telomere uncapping and Rad50-dependent homologous recombination. EMBO J. 2001;20:6127-39 pubmed
    ..We propose that Cdc13 prevents telomere uncapping and inhibits recombination between telomeric sequences through a pathway distinct from and complementary to that used by telomerase. ..
  26. Thorslund T, Esashi F, West S. Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1. EMBO J. 2007;26:2915-22 pubmed
    ..These results lead us to suggest that BRCA2 is a universal regulator of RAD51/DMC1 recombinase actions. ..
  27. Lambert S, Mizuno K, Blaisonneau J, Martineau S, Chanet R, Fréon K, et al. Homologous recombination restarts blocked replication forks at the expense of genome rearrangements by template exchange. Mol Cell. 2010;39:346-59 pubmed publisher
    ..In contrast, we report that the Srs2 helicase promotes both fork restart and template exchange. Our data demonstrate that template exchange occurs during recombination-dependent fork restart at the expense of genome rearrangements. ..
  28. Ploquin M, Bransi A, Paquet E, Stasiak A, Stasiak A, Yu X, et al. Functional and structural basis for a bacteriophage homolog of human RAD52. Curr Biol. 2008;18:1142-6 pubmed publisher
    ..For the first time, we propose a viral homolog of RAD52 at the amino acid, phylogenic, functional, and structural levels. ..
  29. Grimme J, Honda M, Wright R, Okuno Y, Rothenberg E, Mazin A, et al. Human Rad52 binds and wraps single-stranded DNA and mediates annealing via two hRad52-ssDNA complexes. Nucleic Acids Res. 2010;38:2917-30 pubmed publisher
  30. Grimme J, Spies M. FRET-based assays to monitor DNA binding and annealing by Rad52 recombination mediator protein. Methods Mol Biol. 2011;745:463-83 pubmed publisher
    ..Finally, FRET between Cy3 and Cy5 dyes incorporated into two homologous ssDNA molecules can be used to analyze interplay between Rad52-mediated DNA strand annealing and duplex DNA destabilization by RPA. ..
  31. Shor E, Gangloff S, Wagner M, Weinstein J, Price G, Rothstein R. Mutations in homologous recombination genes rescue top3 slow growth in Saccharomyces cerevisiae. Genetics. 2002;162:647-62 pubmed
    ..We present a model wherein Rad51 helps recruit Sgs1-Top3 to sites of replicative damage. ..
  32. Shen Z, Denison K, Lobb R, Gatewood J, Chen D. 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. Genomics. 1995;25:199-206 pubmed
    ..In addition to an approximately 1.9-kb RAD52 mRNA band that is present in all of the tested tissues, an extra mRNA species of approximately 0.85 kb was detectable in mouse testis. ..
  33. Bai Y, Symington L. A Rad52 homolog is required for RAD51-independent mitotic recombination in Saccharomyces cerevisiae. Genes Dev. 1996;10:2025-37 pubmed
    ..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. ..
  34. Sung P. Function of yeast Rad52 protein as a mediator between replication protein A and the Rad51 recombinase. J Biol Chem. 1997;272:28194-7 pubmed
    ..Thus, Rad52 functions as a co-factor for the Rad51 recombinase, acting specifically to overcome the apparent competition by RPA for binding to single-stranded DNA. ..
  35. Lisby M, Rothstein R, Mortensen U. Rad52 forms DNA repair and recombination centers during S phase. Proc Natl Acad Sci U S A. 2001;98:8276-82 pubmed
    ..Furthermore, our data indicate that each Rad52 focus represents a center of recombinational repair capable of processing multiple DNA lesions. ..
  36. Jackson D, Dhar K, Wahl J, Wold M, Borgstahl G. Analysis of the human replication protein A:Rad52 complex: evidence for crosstalk between RPA32, RPA70, Rad52 and DNA. J Mol Biol. 2002;321:133-48 pubmed
    ..Implications for these results for the "hand-off" mechanism between protein-protein partners, including Rad51, in homologous recombination and single-strand annealing are discussed. ..
  37. Versini G, Comet I, Wu M, Hoopes L, Schwob E, Pasero P. The yeast Sgs1 helicase is differentially required for genomic and ribosomal DNA replication. EMBO J. 2003;22:1939-49 pubmed
    ..These data suggest that Sgs1p is not required for processive DNA synthesis but prevents genomic instability by coordinating replication and recombination events during S phase. ..
  38. Lisby M, Antúnez de Mayolo A, Mortensen U, Rothstein R. Cell cycle-regulated centers of DNA double-strand break repair. Cell Cycle. 2003;2:479-83 pubmed
    ..Interestingly, in a small but significant fraction of the S phase cells, the two ends of a break separate suggesting that mechanisms exist to reassociate and align these ends for proper DNA repair. ..
  39. Ma J, Kim E, Haber J, Lee S. Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. Mol Cell Biol. 2003;23:8820-8 pubmed
    ..The increased gamma ray sensitivity of rad1Delta rad52Delta yku70Delta strains compared to rad52Delta yku70Delta strains suggests that MMEJ also contributes to the repair of DSBs induced by ionizing radiation. ..
  40. Daley J, Wilson T. Rejoining of DNA double-strand breaks as a function of overhang length. Mol Cell Biol. 2005;25:896-906 pubmed
    ..These data support a model in which annealing energy is a primary determinant of the rejoining efficiency and mechanism. ..
  41. Pohl T, Nickoloff J. Rad51-independent interchromosomal double-strand break repair by gene conversion requires Rad52 but not Rad55, Rad57, or Dmc1. Mol Cell Biol. 2008;28:897-906 pubmed
  42. Galli A, Cervelli T, Schiestl R. Characterization of the hyperrecombination phenotype of the pol3-t mutation of Saccharomyces cerevisiae. Genetics. 2003;164:65-79 pubmed
  43. Lopes J, Ribeyre C, Nicolas A. Complex minisatellite rearrangements generated in the total or partial absence of Rad27/hFEN1 activity occur in a single generation and are Rad51 and Rad52 dependent. Mol Cell Biol. 2006;26:6675-89 pubmed
  44. Tsukamoto M, Yamashita K, Miyazaki T, Shinohara M, Shinohara A. The N-terminal DNA-binding domain of Rad52 promotes RAD51-independent recombination in Saccharomyces cerevisiae. Genetics. 2003;165:1703-15 pubmed
    ..These findings indicate that Rad52 itself, and more precisely its N-terminal DNA-binding domain, promote an essential reaction in recombination in the absence of RAD51. ..
  45. Tsai Y, Tseng S, Chang S, Lin C, Teng S. Involvement of replicative polymerases, Tel1p, Mec1p, Cdc13p, and the Ku complex in telomere-telomere recombination. Mol Cell Biol. 2002;22:5679-87 pubmed
  46. Krejci L, Macris M, Li Y, Van Komen S, Villemain J, Ellenberger T, et al. Role of ATP hydrolysis in the antirecombinase function of Saccharomyces cerevisiae Srs2 protein. J Biol Chem. 2004;279:23193-9 pubmed
    ..These results highlight the importance of the ATP hydrolysisfueled DNA motor activity in SRS2 functions. ..
  47. Liu Y, Maizels N. Coordinated response of mammalian Rad51 and Rad52 to DNA damage. EMBO Rep. 2000;1:85-90 pubmed
    ..These observations provide evidence of coordinated function of Rad51 and Rad52 in vivo and support the hypothesis that Rad52 plays an important role in the DNA damage response in mammalian cells. ..
  48. Moriel Carretero M, Aguilera A. A postincision-deficient TFIIH causes replication fork breakage and uncovers alternative Rad51- or Pol32-mediated restart mechanisms. Mol Cell. 2010;37:690-701 pubmed publisher
    ..Our results define the genetic and molecular hallmarks of replication fork breakage and restart and bring insights to understand specific NER-related human syndromes. ..
  49. Lloyd J, McGrew D, Knight K. Identification of residues important for DNA binding in the full-length human Rad52 protein. J Mol Biol. 2005;345:239-49 pubmed
  50. Chan J, Kolodner R. A genetic and structural study of genome rearrangements mediated by high copy repeat Ty1 elements. PLoS Genet. 2011;7:e1002089 pubmed publisher
  51. Antúnez de Mayolo A, Lisby M, Erdeniz N, Thybo T, Mortensen U, Rothstein R. Multiple start codons and phosphorylation result in discrete Rad52 protein species. Nucleic Acids Res. 2006;34:2587-97 pubmed
    ..We also show that the Rad52 protein can be translated from the last three start sites and expression from any one of them is sufficient for spontaneous recombination and the repair of gamma-ray-induced double-strand breaks. ..
  52. 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;3:145-56 pubmed
    ..The interaction of Rad52 with RPA plays an important role in the enhancement of annealing of complementary ssDNAs. We therefore propose that Rad52 mediates the RAD51-independent recombination through an ssDNA annealing, assisted by RPA. ..
  53. Arai N, Kagawa W, Saito K, Shingu Y, Mikawa T, Kurumizaka H, et al. Vital roles of the second DNA-binding site of Rad52 protein in yeast homologous recombination. J Biol Chem. 2011;286:17607-17 pubmed publisher
    ..Our studies suggest that Rad52 within the complex associates with double-stranded DNA to assist Rad51-mediated homologous pairing. ..