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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Powell, Simon N. Feng, Zhihui Scott, Shaun P. Sharma, Girdhar G. Guo, Gongshe Pandita, Tej K. Bussen, Wendy |
| Description | Author Affiliation: Feng Z ( Department of Radiation Oncology, Washington University, St. Louis, MO 63108, USA.); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 2 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | BRCA2 Protein Genetics Gene Expression Regulation, Neoplastic Rad51 Recombinase Metabolism Rad52 DNA Repair And Recombination Protein Cell Line, Tumor Cell Nucleus Chromosomal Instability Chromosome Aberrations DNA Damage Genetic Complementation Test HeLa Cells Microscopy, Fluorescence Tetrazolium Salts Pharmacology Thiazoles Research Support, N.I.H., Extramural Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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