A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination

被引：196

作者：

Zhao, Guang Yu

Sonoda, Eiichiro

Barber, Louise J.

Oka, Hayato

Murakawa, Yasuhiro

Yamada, Kouichi

Ikura, Tsuyoshi

Wang, Xin

Kobayashi, Masahiko

Yamamoto, Kenichi

Boulton, Simon J.

Takeda, Shunichi

机构：

[1] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, CREST Lab,Sakyo Ku, Kyoto 6068501, Japan

[2] Canc Res UK, London Res UK, Clare Hall Labs, S Mimms EN6 3LD, Herts, England

[3] Natl Inst Hlth & Nutr, Div Geriatr Hlth Sci, Tokyo 1628636, Japan

[4] Tohoku Univ, Grad Sch Med, Dept Biochem, Aoba Ku, Sendai, Miyagi 9808575, Japan

[5] Kanazawa Univ, Canc Res Inst, Dept Mol Pathol, Ishikawa 9200934, Japan

来源：

MOLECULAR CELL | 2007年 / 25卷 / 05期

关键词：

D O I：

10.1016/j.molcel.2007.01.029

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：

The ubiquitin (Ub)-conjugating enzyme Ubc13 is implicated in Rad6/Rad18-dependent post-replication repair (PRR) in budding yeast, but its function in vertebrates is not known. We show here that disruption or siRNA depletion of UBC13 in chicken DT40 or human cells confers severe growth defects due to chromosome instability, and hypersensitivity to both UV and ionizing radiation, consistent with a conserved role for Ubc13 in PRR. Remarkably, Ubc13-deficient cells are also compromised for DNA double-strand break (DSB) repair by homologous recombination (HR). Recruitment and activation of the E3 Ub ligase function of BRCA1 and the subsequent formation of the Rad51 nucleoprotein filament at DSBs are abolished in Ubc13-deficient cells. Furthermore, generation of ssDNA/RPA complexes at DSBs is severely attenuated in the absence of Ubc13. These data reveal a critical and unexpected role for vertebrate Ubc13 in the initiation of HR at the level of DSB processing.

引用

页码：663 / 675

页数：13

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[1] Loss of nonhomologous end joining confers camptothecin resistance in DT40 cells - Implications for the repair of topoisomerase I-mediated DNA damage [J].