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Mouse Rif1 is a key regulator of the replication‐timing programme in mammalian cells
Author(s) -
Cornacchia Daniela,
Dileep Vishnu,
Quivy JeanPierre,
Foti Rossana,
Tili Federico,
SantarellaMellwig Rachel,
Antony Claude,
Almouzni Geneviève,
Gilbert David M,
Buonomo Sara B C
Publication year - 2012
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.214
Subject(s) - biology , replication timing , dna replication , chromatin , origin recognition complex , genetics , microbiology and biotechnology , heterochromatin , transcriptional regulation , dna , eukaryotic dna replication , gene , gene expression
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.