P53 modulates homologous recombination by transcriptional regulation of the RAD51 gene

被引：156

作者：

Arias-Lopez, C

Lazaro-Trueba, I

Kerr, P

Lord, CJ

Dexter, T

Iravani, M

Ashworth, A

Silva, A

机构：

[1] CSIC, Ctr Invest Biol, E-28040 Madrid, Spain

[2] Inst Canc Res, Breakthrough Toby Robins Breast Canc Res Ctr, London SW3 6JB, England

来源：

EMBO REPORTS | 2006年 / 7卷 / 02期

关键词：

p53; Rad51; transcriptional repression; homologous recombination; genome stability;

D O I：

10.1038/sj.embor.7400587

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA repair by homologous recombination is involved in maintaining genome stability. Previous data report that wild-type p53 suppresses homologous recombination and physically interacts with Rad51. Here, we show the in vivo binding of wild-type p53 to a p53 response element in the promoter of Rad51 and the downregulation of Rad51 messenger RNA and protein by wild-type p53, favoured by DNA damage. Moreover, wild-type p53 inhibits Rad51 foci formation in response to double-strand breaks, whereas p53 contact mutant R280K fails to repress Rad51 mRNA and protein expression and Rad51 foci formation. We propose that transcriptional repression of Rad51 by p53 participates in regulating homologous recombination, and impaired Rad51 repression by p53 mutants may contribute to malignant transformation.

引用

页码：219 / 224

页数：6

共 37 条

[1] The proline-rich domain of p53 is required for cooperation with anti-neoplastic agents to promote apoptosis of tumor cells [J].