The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1 |
| |
Authors: | Delacroix Sinny Wagner Jill M Kobayashi Masahiko Yamamoto Ken-ichi Karnitz Larry M |
| |
Institution: | Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|