| Rad52 inactivation is synthetically lethal with BRCA2 deficiency. | |
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MedLine Citation:
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PMID: 21148102 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Zhihui Feng; Shaun P Scott; Wendy Bussen; Girdhar G Sharma; Gongshe Guo; Tej K Pandita; Simon N Powell |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-12-08 |
Journal Detail:
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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:
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Created Date: 2011-01-12 Completed Date: 2011-02-24 Revised Date: 2011-07-20 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 686-91 Citation Subset: IM |
Affiliation:
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Department of Radiation Oncology, Washington University, St. Louis, MO 63108, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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BRCA2 Protein
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genetics* Cell Line, Tumor Cell Nucleus / metabolism Chromosomal Instability Chromosome Aberrations DNA Damage Gene Expression Regulation, Neoplastic* Genetic Complementation Test Hela Cells Humans Microscopy, Fluorescence / methods Rad51 Recombinase / metabolism* Rad52 DNA Repair and Recombination Protein / metabolism* Tetrazolium Salts / pharmacology Thiazoles / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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CA107640/CA/NCI NIH HHS; CA123232/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 |
| Comments/Corrections | |
Comment In:
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Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):441-2
[PMID:
21189297
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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