NCOA4 transcriptional coactivator inhibits activation of DNA replication origins. (Articolo in rivista)

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  • NCOA4 transcriptional coactivator inhibits activation of DNA replication origins. (Articolo in rivista) (literal)
Anno
  • 2014-01-01T00:00:00+01:00 (literal)
Alternative label
  • Bellelli R1, Castellone MD1, Guida T1, Limongello R1, Dathan NA2, Merolla F1, Cirafici AM1, Affuso A3, Masai H4, Costanzo V5, Grieco D1, Fusco A1, Santoro M6, Carlomagno F7. (2014)
    NCOA4 transcriptional coactivator inhibits activation of DNA replication origins.
    in Molecular cell (Online)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Bellelli R1, Castellone MD1, Guida T1, Limongello R1, Dathan NA2, Merolla F1, Cirafici AM1, Affuso A3, Masai H4, Costanzo V5, Grieco D1, Fusco A1, Santoro M6, Carlomagno F7. (literal)
Rivista
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1Istituto di Endocrinologia ed Oncologia Sperimentale del CNR/Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli \"Federico II,\" 80131 Naples, Italy. 2Istituto di Biostrutture e Bioimmagini del CNR, 80134 Naples, Italy. 3Animal Model Facility, Biogem s.c.a.r.l., 83031 Ariano Irpino, Avellino, Italy. 4Tokyo Metropolitan Institute of Medical Sciences, 156-8506 Tokyo, Japan. 5London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms EN6 3LD, UK. 6Istituto di Endocrinologia ed Oncologia Sperimentale del CNR/Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli \"Federico II,\" 80131 Naples, Italy. Electronic address: masantor@unina.it. 7Istituto di Endocrinologia ed Oncologia Sperimentale del CNR/Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli \"Federico II,\" 80131 Naples, Italy. Electronic address: persfra@tin.it. (literal)
Titolo
  • NCOA4 transcriptional coactivator inhibits activation of DNA replication origins. (literal)
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. (literal)
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