Document Detail

Rad52 inactivation is synthetically lethal with BRCA2 deficiency.
MedLine Citation:
PMID:  21148102     Owner:  NLM     Status:  MEDLINE    
Synthetic lethality is a powerful approach to study selective cell killing based on genotype. We show that loss of Rad52 function is synthetically lethal with breast cancer 2, early onset (BRCA2) deficiency, whereas there was no impact on cell growth and viability in BRCA2-complemented cells. The frequency of both spontaneous and double-strand break-induced homologous recombination and ionizing radiation-induced Rad51 foci decreased by 2-10 times when Rad52 was depleted in BRCA2-deficient cells, with little to no effect in BRCA2-complemented cells. The absence of both Rad52 and BRCA2 resulted in extensive chromosome aberrations, especially chromatid-type aberrations. Ionizing radiation-induced and S phase-associated Rad52-Rad51 foci form equally well in the presence or absence of BRCA2, indicating that Rad52 can respond to DNA double-strand breaks and replication stalling independently of BRCA2. Rad52 thus is an independent and alternative repair pathway of homologous recombination and a target for therapy in BRCA2-deficient cells.
Zhihui Feng; Shaun P Scott; Wendy Bussen; Girdhar G Sharma; Gongshe Guo; Tej K Pandita; Simon N Powell
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-12-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  108     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-12     Completed Date:  2011-02-24     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  686-91     Citation Subset:  IM    
Department of Radiation Oncology, Washington University, St. Louis, MO 63108, USA.
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MeSH Terms
BRCA2 Protein / genetics*
Cell Line, Tumor
Cell Nucleus / metabolism
Chromosomal Instability
Chromosome Aberrations
DNA Damage
Gene Expression Regulation, Neoplastic*
Genetic Complementation Test
HeLa Cells
Microscopy, Fluorescence / methods
Rad51 Recombinase / metabolism*
Rad52 DNA Repair and Recombination Protein / metabolism*
Tetrazolium Salts / pharmacology
Thiazoles / pharmacology
Grant Support
Reg. No./Substance:
0/BRCA2 Protein; 0/BRCA2 protein, human; 0/RAD52 protein, human; 0/Rad52 DNA Repair and Recombination Protein; 0/Tetrazolium Salts; 0/Thiazoles; 298-93-1/thiazolyl blue; EC 2.7.7.-/RAD51 protein, human; EC 2.7.7.-/Rad51 Recombinase
Comment In:
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):441-2   [PMID:  21189297 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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