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Review
. 2012 Dec 1;18(23):6400-6.
doi: 10.1158/1078-0432.CCR-11-3150. Epub 2012 Oct 15.

Molecular pathways: understanding the role of Rad52 in homologous recombination for therapeutic advancement

Benjamin H Lok  1 , Simon N Powell
Affiliations
Review

Molecular pathways: understanding the role of Rad52 in homologous recombination for therapeutic advancement

Benjamin H Lok et al. Clin Cancer Res. .

Abstract

The Rad52 protein was largely ignored in humans and other mammals when the mouse knockout revealed a largely "no-effect" phenotype. However, using synthetic lethal approaches to investigate context-dependent function, new studies have shown that Rad52 plays a key survival role in cells lacking the function of the breast cancer type 1 susceptibility protein (BRCA1)-BRCA2 pathway of homologous recombination. Biochemical studies also showed significant differences between yeast and human Rad52 (hRad52), in which yeast Rad52 can promote strand invasion of replication protein A (RPA)-coated single-stranded DNA (ssDNA) in the presence of Rad51 but hRad52 cannot. This results in the paradox of how is hRad52 providing Rad51 function: presumably there is something missing in the biochemical assays that exists in vivo, but the nature of this missing factor is currently unknown. Recent studies have suggested that Rad52 provides back-up Rad51 function for all members of the BRCA1-BRCA2 pathway, suggesting that Rad52 may be a target for therapy in BRCA pathway-deficient cancers. Screening for ways to inhibit Rad52 would potentially provide a complementary strategy for targeting BRCA-deficient cancers in addition to poly (ADP-ribose) polymerase (PARP) inhibitors.

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Conflict of interest statement

Conflicts of interest.

The authors have no potential conflict of interest to report.

Figures

Fig 1
Fig 1
The BRCA and RAD52 pathways of DNA double-strand break (DSB) repair. Various DNA lesions lead to DSBs that can be repaired by homologous recombination (HR) or single-strand annealing (SSA). A) In the HR pathway, after activation of the DNA damage response pathway, DNA ends are resected to expose 3’ single-stranded DNA (ssDNA) which become substrates for binding by RPA. BRCA2 or, in its absence, Rad52 can recruit Rad51 for loading onto ssDNA, displacing RPA, allowing for homology searching and strand invasion by the Rad51 nucleofilament. Subsequently, noncrossover or crossover ligation products are generated in the double-strand break repair (DSBR) pathway or only noncrossover products when synthesis-dependent strand-annealing (SDSA) is utilized. B) SSA requires repetitive sequences around the DSB. After resection, Rad52 mediates annealing of the exposed complementary sequences. After removal of the 3’-flaps, ligation leads to repair, with loss of the intervening sequence. *There is currently no clear evidence that 1-end DSBs or daughter-strand gaps are repaired by single-strand annealing. The left half of panel A is adapted by permission from Macmillan Publishers Ltd: Nature Reviews Molecular Cell Biology (66), copyright 2006.
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References

    1. Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. [Internet] [cited 2012 Apr 23];Science (New York, N.Y.) 1995 Jun;268(5218):1749–1753. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7792600. - PubMed
    1. Stewart GS, Maser RS, Stankovic T, Bressan DA, Kaplan MI, Jaspers NG, et al. [Internet] [cited 2012 Apr 23];Cell. 1999 Dec;99(6):577–587. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10612394. - PubMed
    1. Roy R, Chun J, Powell SN. BRCA1 and BRCA2: different roles in a common pathway of genome protection. [Internet] Nature reviews. Cancer. 2012 Jan;12(1):68–78. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22193408. - PMC - PubMed
    1. Symington LS. Role of RAD52 Epistasis Group Genes in Homologous Recombination and Double-Strand Break Repair [Internet] Microbiology and Molecular Biology Reviews. 2002;66(4):630–670. table of contents.Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=134659&tool=pm.... - PMC - PubMed
    1. McEachern MJ, Haber JE. Break-induced replication and recombinational telomere elongation in yeast. [Internet] [cited 2012 Mar 16];Annual review of biochemistry. 2006 Jan;75:111–135. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16756487. - PubMed

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