A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome.

2.50
Hdl Handle:
http://hdl.handle.net/10541/109323
Title:
A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome.
Authors:
Gambus, Agnieszka; Van Deursen, Frederick; Polychronopoulos, Dimitrios; Foltman, Magdalena; Jones, Richard C; Edmondson, Ricky D; Calzada, Arturo; Labib, Karim
Abstract:
The 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.
Affiliation:
Cancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
Citation:
A 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.
Journal:
The EMBO Journal
Issue Date:
7-Oct-2009
URI:
http://hdl.handle.net/10541/109323
DOI:
10.1038/emboj.2009.226
PubMed ID:
19661920
Type:
Article
Language:
en
ISSN:
1460-2075
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorGambus, Agnieszkaen
dc.contributor.authorVan Deursen, Fredericken
dc.contributor.authorPolychronopoulos, Dimitriosen
dc.contributor.authorFoltman, Magdalenaen
dc.contributor.authorJones, Richard Cen
dc.contributor.authorEdmondson, Ricky Den
dc.contributor.authorCalzada, Arturoen
dc.contributor.authorLabib, Karimen
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.en
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
All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.