ATP-dependent chromatin remodeling factors tune S phase checkpoint activity.
Publication Type:
Journal ArticleSource:
Molecular and cellular biology, Volume 31, Issue 22, p.4454-63 (2011)Keywords:
2011, Basic Sciences Division, Center-Authored Paper, October 2011Abstract:
The S phase checkpoint response slows down replication in the presence of replication stress such that replication can resume normally once conditions are favorable. Both proper activation and deactivation of the checkpoint are crucial for genome stability. However, mechanisms of checkpoint deactivation have been largely unknown. Here, we show that two highly conserved Saccharomyces cerevisiae ATP-dependent chromatin-remodeling factors, Isw2 and Ino80, function to attenuate and deactivate S phase checkpoint activity. Genetic interactions revealed that these chromatin remodeling factors and the Rad53 phosphatases function in parallel in the DNA replication stress response. Following a transient replication stress, a double mutant isw2 nhp10 displays stronger and prolonged checkpoint activation without experiencing increased replication fork troubles. Isw2 and Ino80 are both enriched at stalled replication forks, and physically and specifically interact with single-stranded DNA binding protein (RPA). Based on these results, we propose that Isw2 and Ino80 are targeted to stalled replication forks via RPA and directly control the amplitude of S phase checkpoint activity and the subsequent deactivation process.
Doing Business with Arnold Library
Weintraub Building, B1-010
(206) 667-4314
library@fredhutch.org
More About Arnold Library
Quick Links
- ILLiad/ILL Form
- Journals List
- Ovid - Medline
- Web of Science
- Pubmed
- Libguides
- Library Catalog
- Researcher Profiles
- Library Affiliations & Memberships
- Fred Hutch Papers (Intranet)