Enhancement of RAD51 recombinase activity by the tumor suppressor PALB2

被引：126

作者：

Dray, Eloiese ^{[1
]}

Etchin, Julia ^{[1
]}

Wiese, Claudia ^{[2
]}

Saro, Dorina ^{[1
]}

Williams, Gareth J. ^{[2
]}

Hammel, Michal ^{[2
]}

Yu, Xiong ^{[3
]}

Galkin, Vitold E. ^{[3
]}

Liu, Dongqing ^{[1
]}

Tsai, Miaw-Sheue ^{[2
]}

Sy, Shirley M-H ^{[4
]}

Schild, David ^{[2
]}

Egelman, Edward ^{[3
]}

Chen, Junjie ^{[4
]}

Sung, Patrick ^{[1
]}

机构：

[1] Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06510 USA

[2] Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA

[3] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA

[4] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06510 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2010年 / 17卷 / 10期

基金：

美国国家卫生研究院;

关键词：

HOMOLOGOUS RECOMBINATION; FANCONI-ANEMIA; BREAST-CANCER; BRCA2; COMPLEX; INSTABILITY; MUTATIONS; EXCHANGE; PARTNER; PROTEIN;

D O I：

10.1038/nsmb.1916

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：

Homologous recombination mediated by RAD51 recombinase helps eliminate chromosomal lesions, such as DNA double-strand breaks induced by radiation or arising from injured DNA replication forks. The tumor suppressors BRCA2 and PALB2 act together to deliver RAD51 to chromosomal lesions to initiate repair. Here we document a new function of PALB2: to enhance RAD51's ability to form the D loop. We show that PALB2 binds DNA and physically interacts with RAD51. Notably, although PALB2 alone stimulates D-loop formation, it has a cooperative effect with RAD51AP1, an enhancer of RAD51. This stimulation stems from the ability of PALB2 to function with RAD51 and RAD51AP1 to assemble the synaptic complex. Our results demonstrate the multifaceted role of PALB2 in chromosome damage repair. Because PALB2 mutations can cause cancer or Fanconi anemia, our findings shed light on the mechanism of tumor suppression in humans.

引用

页码：1255 / +

页数：6

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