NCOA4 transcriptional coactivator inhibits activation of DNA replication origins
Open accessAbstract
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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References 54 · Cited by 66
- Authors
- Bellelli, R., Castellone, M. D., Guida, T., Limongello, R., Dathan, N. A., Merolla, F., Cirafici, A. M., Affuso, A., Masai, H., Costanzo, V., Grieco, D., Fusco, A., Santoro, M., & Carlomagno, F.
- Affiliations
- Institute for Experimental Endocrinology and Oncology (IT)
- Institute of Biostructure and Bioimaging (IT)
- Biogem (IT)
- Tokyo Metropolitan Institute of Medical Science (JP)
- Corresponding author
- Santoro, Massimo
- Carlomagno, Francesca
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 55
- Issue
- 1
- Pages
- 123-137
- ISSN
- 1097-2765 (ISSN-L)
- OpenAlex
- W2066374073
- Cited by
- 66
- References
- 54
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 12 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 12 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 3 · 2015: 3 · 2014: 2
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
- Funders
- Associazione Italiana per la Ricerca sul Cancro
- Shanghai Ocean University
- Japan Society for the Promotion of Science (23657081)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- NCOA4, transcriptional coactivator, MCM7, CMG helicase, replication stress, premature senescence, minichromosome maintenance proteins, nuclear receptors, DNA synthesis regulation
- MeSH terms
- Animals, Cells, Cultured, DNA Replication, HeLa Cells, Humans, Xenopus laevis, Cellular Senescence, Replication Origin, Two-Hybrid System Techniques, Mice, Nuclear Receptor Coactivators, Minichromosome Maintenance Complex Component 7
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