Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 55 (1), 123-37

NCOA4 Transcriptional Coactivator Inhibits Activation of DNA Replication Origins

Affiliations

NCOA4 Transcriptional Coactivator Inhibits Activation of DNA Replication Origins

Roberto Bellelli et al. Mol Cell.

Abstract

NCOA4 is a transcriptional coactivator of nuclear hormone receptors that undergoes gene rearrangement in human cancer. By combining studies in Xenopus laevis egg extracts and mouse embryonic fibroblasts (MEFs), we show here that NCOA4 is a minichromosome maintenance 7 (MCM7)-interacting protein that is able to control DNA replication. Depletion-reconstitution experiments in Xenopus laevis egg extracts indicate that NCOA4 acts as an inhibitor of DNA replication origin activation by regulating CMG (CDC45/MCM2-7/GINS) helicase. NCOA4(-/-) MEFs display unscheduled origin activation and reduced interorigin distance; this results in replication stress, as shown by the presence of fork stalling, reduction of fork speed, and premature senescence. Together, our findings indicate that NCOA4 acts as a regulator of DNA replication origins that helps prevent inappropriate DNA synthesis and replication stress.

Similar articles

See all similar articles

Cited by 18 articles

See all "Cited by" articles

Publication types

Substances

LinkOut - more resources

Feedback