期刊
GENES & DEVELOPMENT
卷 21, 期 12, 页码 1472-1477出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1547007
关键词
checkpoint; replication; Rad9; ATR; TopBP1; Chk1
资金
- NCI NIH HHS [R56 CA084321, R01 CA084321, R01 CA84321] Funding Source: Medline
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.
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