Journal
EMBO JOURNAL
Volume 31, Issue 18, Pages 3678-3690Publisher
WILEY
DOI: 10.1038/emboj.2012.214
Keywords
chromatin organization; DNA replication; genome stability; replication timing; Rif1
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Funding
- la Ligue Nationale contre le Cancer (Equipe labellisee Ligue)
- European Commission Network of Excellence EpiGeneSys [HEALTH-F4-2010-257082]
- ERC [2009-AdG_20090506 'Eccentric']
- ANR 'ECenS' [ANR-09-BLAN-0257-01]
- EMBL Interdisciplinary Postdoc (EIPOD) under Marie Curie Actions (COFUND)
- EpiGeneSys Network of Excellence
- Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0257] Funding Source: Agence Nationale de la Recherche (ANR)
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The eukaryotic genome is replicated according to a specific spatio-temporal programme. However, little is known about both its molecular control and biological significance. Here, we identify mouse Rif1 as a key player in the regulation of DNA replication timing. We show that Rif1 deficiency in primary cells results in an unprecedented global alteration of the temporal order of replication. This effect takes place already in the first S-phase after Rif1 deletion and is neither accompanied by alterations in the transcriptional landscape nor by major changes in the biochemical identity of constitutive heterochromatin. In addition, Rif1 deficiency leads to both defective G1/S transition and chromatin re-organization after DNA replication. Together, these data offer a novel insight into the global regulation and biological significance of the replication-timing programme in mammalian cells. The EMBO Journal (2012) 31, 3678-3690. doi: 10.1038/emboj.2012.214; Published online 31 July 2012
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