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

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...

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Bibliographic Details
Published in:The EMBO journal 2009-10, Vol.28 (19), p.2992
Main Authors: Gambus, Agnieszka, Van Deursen, Frederick, Polychronopoulos, Dimitrios, Foltman, Magdalena, Jones, Richard C, Edmondson, Ricky D, Calzada, Arturo, Labib, Karim
Format: Article
Language:English
Subjects:
Cell cycle
Chromosomes
Deoxyribonucleic acid
DNA
DNA polymerase
Genomics
Molecular biology
Yeasts
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Summary: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. [PUBLICATION ABSTRACT]
ISSN:0261-4189
1460-2075
DOI:10.1038/emboj.2009.226