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XB-ART-49125
Mol Cell 2014 Jul 03;551:123-37. doi: 10.1016/j.molcel.2014.04.031.
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NCOA4 transcriptional coactivator inhibits activation of DNA replication origins.

Bellelli R , Castellone MD , Guida T , Limongello R , Dathan NA , Merolla F , Cirafici AM , Affuso A , Masai H , Costanzo V , Grieco D , Fusco A , Santoro M , Carlomagno F .


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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.

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Species referenced: Xenopus laevis
Genes referenced: cdc45 mcm2 mcm3 mcm4 mcm5 mcm7 ncoa4