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dc.contributor.authorGambus, Agnieszka
dc.contributor.authorVan Deursen, Frederick
dc.contributor.authorPolychronopoulos, Dimitrios
dc.contributor.authorFoltman, Magdalena
dc.contributor.authorJones, Richard C
dc.contributor.authorEdmondson, Ricky D
dc.contributor.authorCalzada, Arturo
dc.contributor.authorLabib, Karim
dc.date.accessioned2010-08-09T14:46:10Z
dc.date.available2010-08-09T14:46:10Z
dc.date.issued2009-10-07
dc.identifier.citationA key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome. 2009, 28 (19):2992-3004 EMBO J.en
dc.identifier.issn1460-2075
dc.identifier.pmid19661920
dc.identifier.doi10.1038/emboj.2009.226
dc.identifier.urihttp://hdl.handle.net/10541/109323
dc.description.abstractThe eukaryotic replisome is a crucial determinant of genome stability, but its structure is still poorly understood. We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components. Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. We show that cells lacking both Ctf4 and Mrc1 experience chronic activation of the DNA damage checkpoint during chromosome replication and do not complete the cell cycle. These findings indicate that coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this process.
dc.language.isoenen
dc.subject.meshCell Cycle
dc.subject.meshCell Cycle Proteins
dc.subject.meshChromosomal Proteins, Non-Histone
dc.subject.meshDNA
dc.subject.meshDNA Polymerase I
dc.subject.meshDNA Replication
dc.subject.meshDNA-Binding Proteins
dc.subject.meshFungal Proteins
dc.subject.meshNuclear Proteins
dc.subject.meshProtein Binding
dc.subject.meshSaccharomyces cerevisiae
dc.subject.meshSaccharomyces cerevisiae Proteins
dc.titleA key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.en
dc.identifier.journalThe EMBO Journalen
html.description.abstractThe eukaryotic replisome is a crucial determinant of genome stability, but its structure is still poorly understood. We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components. Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. We show that cells lacking both Ctf4 and Mrc1 experience chronic activation of the DNA damage checkpoint during chromosome replication and do not complete the cell cycle. These findings indicate that coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this process.


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