Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining.

Xia F; Taghian DG; DeFrank JSZeng ZCWillers HIliakis GPowell SN

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining.

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Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining.

机译：Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining.

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Carriers of BRCA2 germline mutations are at high risk to develop early-onset breast cancer. The underlying mechanisms of how BRCA2 inactivation predisposes to malignant transformation have not been established. Here, we provide direct functional evidence that human BRCA2 promotes homologous recombination (HR), which comprises one major pathway of DNA double-strand break repair. We found that up-regulated HR after transfection of wild-type (wt) BRCA2 into a human tumor line with mutant BRCA2 was linked to increased radioresistance. In addition, BRCA2-mediated enhancement of HR depended on the interaction with Rad51. In contrast to the tumor suppressor BRCA1, which is involved in multiple DNA repair pathways, BRCA2 status had no impact on the other principal double-strand break repair pathway, nonhomologous end joining. Thus, there exists a specific regulation of HR by BRCA2, which may function to maintain genomic integrity and suppress tumor development in proliferating cells.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2001年第15期|8644-8649|共6页
作者
Xia F; Taghian DG; DeFrank JSZeng ZCWillers HIliakis GPowell SN;
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作者单位

Laboratory of Molecular and Cellular Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.;

brc.edu;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Neoplasm Proteins; Recombination; Genetic; Transcription Factors; BRCA2-protein; 肿瘤蛋白质类; 重组; 遗传; 转录因子;

Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining.

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