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PMID: 23071261 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

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

Clinical cancer research : an official journal of the American Association for Cancer Research ·Vol. 18 ·No. 23 ·2012-12-01 ·Pages 6400-6

Lok BH, Powell SN

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.

MeSH Terms
Animals BRCA1 Protein/deficiency,genetics,metabolism BRCA2 Protein/deficiency,genetics,metabolism Fanconi Anemia Complementation Group N Protein Homologous Recombination Humans Molecular Targeted Therapy Neoplasms/genetics,metabolism,therapy Nuclear Proteins/deficiency,genetics,metabolism Rad51 Recombinase/metabolism Rad52 DNA Repair and Recombination Protein/genetics,metabolism Saccharomyces cerevisiae/genetics,metabolism Signal Transduction Tumor Suppressor Proteins/deficiency,genetics,metabolism
Chemicals
BRCA1 Protein BRCA2 Protein Fanconi Anemia Complementation Group N Protein Nuclear Proteins PALB2 protein, human Rad52 DNA Repair and Recombination Protein Tumor Suppressor Proteins Rad51 Recombinase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Lok Benjamin H
Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Powell Simon N
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Article Info
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
Abbr.
Clin Cancer Res
ISSN
1557-3265
DOI
10.1158/1078-0432.CCR-11-3150
Published
2012-12-01
Epub
2012-00-15
Pages
6400-6
Language
English
Region
United States
NLM ID
9502500
PMCID
PMC3513650
Subset
IM
Grants
NCI NIH HHS · CA58985 · United States
Howard Hughes Medical Institute · 57007004 · United States
NCI NIH HHS · CA86140 · United States
NCI NIH HHS · R01 CA058985 · United States
NCI NIH HHS · R01 CA169306 · United States
External Links
PubMed source DOI: 10.1158/1078-0432.CCR-11-3150 PMC Full Text View journal details
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