PALB2 Links BRCA1 and BRCA2 in the DNA-Damage Response

被引：432

作者：

Zhang, Feng ^{[2
]}

Ma, Jianglin ^{[1
]}

Wu, Jiaxue ^{[2
]}

Ye, Lin ^{[2
]}

Cai, Hong ^{[1
]}

Xia, Bing ^{[1
]}

Yu, Xiaochun ^{[2
]}

机构：

[1] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Radiat Oncol, Canc Inst New Jersey, New Brunswick, NJ 08903 USA

[2] Univ Michigan, Sch Med, Dept Internal Med, Div Mol Med & Genet, Ann Arbor, MI 48109 USA

来源：

CURRENT BIOLOGY | 2009年 / 19卷 / 06期

基金：

美国国家卫生研究院;

关键词：

FANCONI-ANEMIA; CANCER SUSCEPTIBILITY; S-PHASE; PHOSPHORYLATION; ATM; BACH1; RECOMBINATION; CHECKPOINT; PARTNER; PROTEIN;

D O I：

10.1016/j.cub.2009.02.018

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：

BRCA1 and BRCA2 are often mutated in familial breast and ovarian cancer. Both tumor suppressors play key roles in the DNA-damage response [1, 2]. However, it remains unclear whether these two tumor suppressor function together in the same DNA-damage response pathway. Here, we show that BRCA1 associates with BRCA2 through PALB2/FANCN, a major binding partner of BRCA2 [3]. The interaction between BRCA1 and BRCA2 is abrogated in PAL132-deficient Fanconi anemia cells and in the cells depleted of PALB2 by small interfering RNA. Moreover, we show that BRCA1 promotes the concentration of PALB2 and BRCA2 at DNA-damage sites and the interaction between BRCA1 and PALB2 is important for the homologous recombination repair. Taken together, our results indicate that BRCA1 is an upstream regulator of BRCA2 in the DNA-damage response, and PALB2 is the linker between BRCA1 BRCA2.

引用

页码：524 / 529

页数：6

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