The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1

被引：367

作者：

Delacroix, Sinny

Wagner, Jill M.

Kobayashi, Masahiko

Yamamoto, Ken-ichi

Karnitz, Larry M. ^{[1
]}

机构：

[1] Mayo Clin, Coll Med, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA

[2] Mayo Clin, Coll Med, Dept Radiat Oncol, Rochester, MN 55905 USA

[3] Mayo Clin, Coll Med, Div Oncol Res, Rochester, MN 55905 USA

[4] Kanazawa Univ, Dept Mol Pathol, Kanazawa, Ishikawa 9200934, Japan

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

来源：

GENES & DEVELOPMENT | 2007年 / 21卷 / 12期

关键词：

checkpoint; replication; Rad9; ATR; TopBP1; Chk1;

D O I：

10.1101/gad.1547007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

DNA replication stress triggers the activation of Checkpoint Kinase 1 (Chk1) in a pathway that requires the independent chromatin loading of the ATRIP-ATR (ATR-interacting protein/ATM [ataxia-telangiectasia mutated]-Rad3-related kinase) complex and the Rad9- Hus1-Rad1 (9-1-1) clamp. We show that Rad9' s role in Chk1 activation is to bind TopBP1, which stimulates ATR-mediated Chk1 phosphorylation via TopBP1' s activation domain ( AD), a domain that binds and activates ATR. Notably, fusion of the AD to proliferating cell nuclear antigen ( PCNA) or histone H2B bypasses the requirement for the 9-1-1 clamp, indicating that the 9-1-1 clamp's primary role in activating Chk1 is to localize the AD to a stalled replication fork.

引用

收藏

页码：1472 / 1477

页数：6

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