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Gambus A, et al.  (2009) A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome. EMBO J 28(19):2992-3004

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.

Status: Published Type: Journal Article PubMed ID: 19661920

Topics addressed in this paper

Number of different genes curated to this paper: 32

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Topics Genes linked to topics (#1 - 10 )
CDC45 CDC6 CSM3 CTF4 HHF1 HHT1 HTA1 HTA2 HTB1 HTB2
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Cell Cycle Phase Involved blue ball blue ball
Function/Process blue ball
Genetic Interactions blue ball
Mutants/Phenotypes blue ball blue ball
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Topics Genes linked to topics (#11 - 20 )
MCM10 MCM2 MCM3 MCM4 MCM5 MCM6 MCM7 MMS22 MRC1 POB3
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Topics Genes linked to topics (#21 - 30 )
POL1 POL12 PRI1 PRI2 PSF1 PSF2 PSF3 RAD53 SLD5 SPT16
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Topics Genes linked to topics (#31 - 32 )
TOF1 TOP1
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