Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 37, Pages 16090-16095Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1005031107
Keywords
Cdc7; Cdk2; roscovitine; S phase checkpoint
Categories
Funding
- Medical Research Council
- Cancer Research UK
- Swedish Cancer Society
- Swedish Children's Cancer Foundation
- Swedish Research Council
- Swedish Pain Relief Foundation
- MRC [G0700730] Funding Source: UKRI
- Medical Research Council [G0700730] Funding Source: researchfish
Ask authors/readers for more resources
DNA replication starts at initiation sites termed replication origins. Metazoan cells contain many more potential origins than are activated (fired) during each S phase. Origin activation is controlled by the ATR checkpoint kinase and its downstream effector kinase Chk1, which suppresses origin firing in response to replication blocks and during normal S phase by inhibiting the cyclin-dependent kinase Cdk2. In addition to increased origin activation, cells deficient in Chk1 activity display reduced rates of replication fork progression. Here we investigate the causal relationship between increased origin firing and reduced replication fork progression. We use the Cdk inhibitor roscovitine or RNAi depletion of Cdc7 to inhibit origin firing in Chk1-inhibited or RNAi-depleted cells. We report that Cdk inhibition and depletion of Cdc7 can alleviate the slow replication fork speeds in Chk1-deficient cells. Our data suggest that increased replication initiation leads to slow replication fork progression and that Chk1 promotes replication fork progression during normal S phase by controlling replication origin activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available