Ontology highlight
ABSTRACT:
SUBMITTER: Tudzarova S
PROVIDER: S-EPMC5105930 | biostudies-literature | 2016 Nov
REPOSITORIES: biostudies-literature
Tudzarova Slavica S Mulholland Paul P Dey Ayona A Stoeber Kai K Okorokov Andrei L AL Williams Gareth H GH
Cell cycle (Georgetown, Tex.) 20160909 21
DNA replication initiation is a key event in the cell cycle, which is dependent on 2 kinases - CDK2 and CDC7. Here we report a novel mechanism in which p53 induces G1 checkpoint and cell cycle arrest by downregulating CDC7 kinase in response to genotoxic stress. We demonstrate that p53 controls CDC7 stability post-transcriptionally via miR-192/215 and post-translationally via Fbxw7β E3 ubiquitin ligase. The p53-dependent pathway of CDC7 downregulation is interlinked with the p53-p21-CDK2 pathway ...[more]