Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation.
Affiliation
Paterson Institute for Cancer Research, University of Manchester, Manchester, UK.Issue Date
2012
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Show full item recordAbstract
Mcm10 is essential for chromosome replication in eukaryotic cells and was previously thought to link the Mcm2-7 DNA helicase at replication forks to DNA polymerase alpha. Here, we show that yeast Mcm10 interacts preferentially with the fraction of the Mcm2-7 helicase that is loaded in an inactive form at origins of DNA replication, suggesting a role for Mcm10 during the initiation of chromosome replication, but Mcm10 is not a stable component of the replisome subsequently. Studies with budding yeast and human cells indicated that Mcm10 chaperones the catalytic subunit of polymerase alpha and preserves its stability. We used a novel degron allele to inactivate Mcm10 efficiently and this blocked the initiation of chromosome replication without causing degradation of DNA polymerase alpha. Strikingly, the other essential helicase subunits Cdc45 and GINS were still recruited to Mcm2-7 when cells entered S-phase without Mcm10, but origin unwinding was blocked. These findings indicate that Mcm10 is required for a novel step during activation of the Cdc45-MCM-GINS helicase at DNA replication origins.Citation
Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation. 2012, 31 (9):2195-206 EMBO JJournal
The EMBO JournalDOI
10.1038/emboj.2012.69PubMed ID
22433841Type
ArticleLanguage
enISSN
1460-2075ae974a485f413a2113503eed53cd6c53
10.1038/emboj.2012.69