2014
DOI: 10.1016/j.celrep.2014.02.019
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Protein Phosphatase 1 Recruitment by Rif1 Regulates DNA Replication Origin Firing by Counteracting DDK Activity

Abstract: SummaryThe firing of eukaryotic origins of DNA replication requires CDK and DDK kinase activities. DDK, in particular, is involved in setting the temporal program of origin activation, a conserved feature of eukaryotes. Rif1, originally identified as a telomeric protein, was recently implicated in specifying replication timing in yeast and mammals. We show that this function of Rif1 depends on its interaction with PP1 phosphatases. Mutations of two PP1 docking motifs in Rif1 lead to early replication of telome… Show more

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Cited by 171 publications
(236 citation statements)
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“…It was recently reported that Rif1 can erase Mcm2-7 phosphorylation by recruiting the protein phosphatase PP1 to the replisome. Therefore, rif1Δ suppressed a cdc7-1 mutation at 30°C and restored cell growth at that temperature (54,57,58). To investigate whether there was a correspondence between suppression of DDK mutants by rif1Δ and restoration of PFA, we first performed growth analysis and confirmed that rif1Δ could suppress a cdc7-1 mutation at 30°C but not at 37°C (Fig.…”
Section: Deletion Of the Inhibitory Domain In The N-terminal Region Omentioning
confidence: 99%
“…It was recently reported that Rif1 can erase Mcm2-7 phosphorylation by recruiting the protein phosphatase PP1 to the replisome. Therefore, rif1Δ suppressed a cdc7-1 mutation at 30°C and restored cell growth at that temperature (54,57,58). To investigate whether there was a correspondence between suppression of DDK mutants by rif1Δ and restoration of PFA, we first performed growth analysis and confirmed that rif1Δ could suppress a cdc7-1 mutation at 30°C but not at 37°C (Fig.…”
Section: Deletion Of the Inhibitory Domain In The N-terminal Region Omentioning
confidence: 99%
“…In budding yeast, proximity to telomeric heterochromatin is both necessary and sufficient to delay origin firing (Ferguson and Fangman 1992). This effect is regulated by Rif1-dependent recruitment of protein phosphatase I, which may antagonize origin activation by the cyclin-and DBF4-dependent kinases (Lian et al 2011;Davé et al 2014;Hiraga et al 2014;Mattarocci et al 2014). Chromatin structure-in particular, histone deacetylation by Sir2 and Rpd3-also affects the timing of nontelomeric origins (Knott et al 2009(Knott et al , 2012Peace et al 2014;Yoshida et al 2014).…”
mentioning
confidence: 99%
“…The other possibility is that Sgo2 acts at the subtelomeres independently of the knobs. As described in Masai et al's review, the telomere-binding protein Rif1 regulates the replication timing of late origins by interacting with PP1 phosphatase to counteract the action of Dbf4-dependent kinase (DDK) at the initiation step of replication (Davé et al, 2014;Hiraga et al, 2014;Mattarocci et al, 2014). Interestingly, Sgo1 forms a complex with PP2A phosphatase to protect cohesins in S. pombe, S. cerevisiae and mammals (Kitajima et al, 2006;Riedel et al, 2006;Tang et al, 2006;, and human Sgo2 also interacts with PP2A for the protection of cohesion (Tanno et al, 2010).…”
Section: Sgo2 Represses Transcription Of Subtelomeric Genesmentioning
confidence: 99%