Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair

被引：232

作者：

Dong, YS

Hakimi, MA

Chen, XW

Kumaraswamy, E

Cooch, NS

Godwin, AK

Shiekhattar, R

机构：

[1] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA

[2] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA

来源：

MOLECULAR CELL | 2003年 / 12卷 / 05期

关键词：

D O I：

10.1016/S1097-2765(03)00424-6

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：

We have isolated a holoenzyme complex termed BRCC containing BRCA1, BRCA2, and RAD51. BRCC not only displays increased association with p53 following DNA damage but also ubiquitinates p53 in vitro. BRCC36 and BRCC45 are novel components of the complex with sequence homology to a subunit of the signalosome and proteasome complexes. Reconstitution of a recombinant four-subunit complex containing BRCA1/BARD1/BRCC45/BRCC36 revealed an enhanced E3 ligase activity compared to that of BRCA1/BARD1 heterodimer. In vivo, depletion of BRCC36 and BRCC45 by the small interfering RNAs (siRNAs) resulted in increased sensitivity to ionizing radiation and defects in G2/M checkpoint. BRCC36 shows aberrant expression in sporadic breast tumors. These findings identify BRCC as a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage.

引用

页码：1087 / 1099

页数：13

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