Journal
GENES & DEVELOPMENT
Volume 24, Issue 24, Pages 2812-2822Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.608210
Keywords
Cohesin; DNA replication; replication origin; MCM; chromatin loop
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Funding
- Spanish Ministry of Science and Innovation
- Consolider Ingenio 2010
- Fundacion Caja Madrid
- Comunidad de Madrid
- Institut National du Cancer
- Association pour la Recherche sur le Cancer
- Fondation pour la Recherche Medicale
- Basque Government
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Genomic DNA is packed in chromatin fibers organized in higher-order structures within the interphase nucleus. One level of organization involves the formation of chromatin loops that may provide a favorable environment to processes such as DNA replication, transcription, and repair. However, little is known about the mechanistic basis of this structuration. Here we demonstrate that cohesin participates in the spatial organization of DNA replication factories in human cells. Cohesin is enriched at replication origins and interacts with prereplication complex proteins. Down-regulation of cohesin slows down S-phase progression by limiting the number of active origins and increasing the length of chromatin loops that correspond with replicon units. These results give a new dimension to the role of cohesin in the architectural organization of interphase chromatin, by showing its participation in DNA replication.
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