Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 280, Issue 30, Pages 27624-27630Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M502615200
Keywords
-
Categories
Funding
- NCI NIH HHS [R01 CA089406, R01 CA089406-07A2, R01 CA060499-12, R01 CA60499, R01 CA060499] Funding Source: Medline
Ask authors/readers for more resources
The origin recognition complex (ORC) is involved in formation of prereplicative complexes (pre-RCs) on replication origins in the G(1) phase. At the G(1)/S transition, elevated cyclin E-CDK2 activity triggers DNA replication to enter S phase. The CDK cycle works as an engine that drives progression of cell cycle events by successive activation of different types of cyclin-CDK. However, how the CDK cycle is coordinated with replication initiation remains elusive. Here we report that acute depletion of ORC2 by RNA interference (RNAi) arrests cells with low cyclin E-CDK2 activity. This result suggests that loss of a replication initiation protein prevents progression of the CDK cycle in G(1). p27 and p21 proteins accumulate following ORC2 RNAi and are required for the CDK2 inhibition. Restoration of CDK activity by co-depletion of p27 and p21 allows many ORC2-depleted cells to enter S phase and go on to mitosis. However, in some cells the release of the CDK2 block caused catastrophic events like apoptosis. Therefore, the CDK2 inhibition observed following ORC2 RNAi seems to protect cells from premature S phase entry and crisis in DNA replication. These results demonstrate an unexpected role of ORC2 in CDK2 activation, a linkage that could be important for maintaining genomic stability.
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