title: Mouse Rif1 is a key regulator of the replication-timing programme in mammalian cells.
abstract: 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.
authors: EMBL Mouse Biology Unit, Monterotondo, Rome, Italy.
authors: Daniela
authors: D
authors: Cornacchia
authors: Vishnu
authors: V
authors: Dileep
authors: Jean-Pierre
authors: JP
authors: Quivy
authors: Rossana
authors: R
authors: Foti
authors: Federico
authors: F
authors: Tili
authors: Rachel
authors: R
authors: Santarella-Mellwig
authors: Claude
authors: C
authors: Antony
authors: Geneviève
authors: G
authors: Almouzni
authors: David M
authors: DM
authors: Gilbert
authors: Sara B C
authors: SB
authors: Buonomo
mesh_terms: D000483:Alleles; D000818:Animals; D002453:Cell Cycle; D004261:DNA Replication; D005260:Female; D016193:G1 Phase; D005786:Gene Expression Regulation; D016678:Genome; D005838:Genotype; D006570:Heterochromatin / Q000737:chemistry; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000379:methods; D015530:Nuclear Matrix / Q000378:metabolism; D016196:S Phase; D034501:Telomere-Binding Proteins / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D006570:Heterochromatin; C492748:Rif1 protein, mouse; D034501:Telomere-Binding Proteins