A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome.
Van Deursen, Frederick
Jones, Richard C
Edmondson, Ricky D
AffiliationCancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.
MetadataShow full item record
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.
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.
JournalThe EMBO Journal
- A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome.
- Authors: Simon AC, Zhou JC, Perera RL, van Deursen F, Evrin C, Ivanova ME, Kilkenny ML, Renault L, Kjaer S, Matak-Vinković D, Labib K, Costa A, Pellegrini L
- Issue date: 2014 Jun 12
- Ctf4 coordinates the progression of helicase and DNA polymerase alpha.
- Authors: Tanaka H, Katou Y, Yagura M, Saitoh K, Itoh T, Araki H, Bando M, Shirahige K
- Issue date: 2009 Jul
- GINS maintains association of Cdc45 with MCM in replisome progression complexes at eukaryotic DNA replication forks.
- Authors: Gambus A, Jones RC, Sanchez-Diaz A, Kanemaki M, van Deursen F, Edmondson RD, Labib K
- Issue date: 2006 Apr
- Dbf4 and Cdc7 proteins promote DNA replication through interactions with distinct Mcm2-7 protein subunits.
- Authors: Ramer MD, Suman ES, Richter H, Stanger K, Spranger M, Bieberstein N, Duncker BP
- Issue date: 2013 May 24
- Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha.
- Authors: Ricke RM, Bielinsky AK
- Issue date: 2004 Oct 22