RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites

被引：558

作者：

Sobhian, Bijan

Shao, Genze

Lilli, Dana R.

Culhane, Aedin C.

Moreau, Lisa A.

Xia, Bing

Livingston, David M.

Greenberg, Roger A.

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[4] Univ Penn, Sch Med, Dept Canc Biol, Philadelphia, PA 19104 USA

[5] Univ Penn, Sch Med, Dept Pathol, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

[6] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[7] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA

来源：

SCIENCE | 2007年 / 316卷 / 5828期

关键词：

D O I：

10.1126/science.1139516

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Mutations affecting the BRCT domains of the breast cancer-associated tumor suppressor BRCA1 disrupt the recruitment of this protein to DNA double-strand breaks (DSBs). The molecular structures at DSBs recognized by BRCA1 are presently unknown. We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-gamma H2AX- dependent lysine(6)- and lysine(63)-linked ubiquitin polymers at DSBs. These events are required for cell cycle checkpoint and repair responses to ionizing radiation, implicating ubiquitin chain recognition and turnover in the BRCA1-mediated repair of DSBs.

引用

收藏

页码：1198 / 1202

页数：5

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