You are here

Mcm10 coordinates the timely assembly and activation of the replication fork helicase.

Title: Mcm10 coordinates the timely assembly and activation of the replication fork helicase.
7 views
0 downloads
Name(s): Perez-Arnaiz, Patricia, author
Bruck, Irina, author
Kaplan, Daniel L, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2016-01-08
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Mcm10 is an essential replication factor that is required for DNA replication in eukaryotes. Two key steps in the initiation of DNA replication are the assembly and activation of Cdc45-Mcm2-7-GINS (CMG) replicative helicase. However, it is not known what coordinates helicase assembly with helicase activation. We show in this manuscript, using purified proteins from budding yeast, that Mcm10 directly interacts with the Mcm2-7 complex and Cdc45. In fact, Mcm10 recruits Cdc45 to Mcm2-7 complex in vitro. To study the role of Mcm10 in more detail in vivo we used an auxin inducible degron in which Mcm10 is degraded upon addition of auxin. We show in this manuscript that Mcm10 is required for the timely recruitment of Cdc45 and GINS recruitment to the Mcm2-7 complex in vivo during early S phase. We also found that Mcm10 stimulates Mcm2 phosphorylation by DDK in vivo and in vitro. These findings indicate that Mcm10 plays a critical role in coupling replicative helicase assembly with helicase activation. Mcm10 is first involved in the recruitment of Cdc45 to the Mcm2-7 complex. After Cdc45-Mcm2-7 complex assembly, Mcm10 promotes origin melting by stimulating DDK phosphorylation of Mcm2, which thereby leads to GINS attachment to Mcm2-7.
Identifier: FSU_pmch_26582917 (IID), 10.1093/nar/gkv1260 (DOI), PMC4705653 (PMCID), 26582917 (RID), 26582917 (EID), gkv1260 (PII)
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4705653.
Subject(s): Cell Cycle Proteins/metabolism
Cell Proliferation
DNA Helicases/metabolism
DNA Replication
DNA-Binding Proteins/metabolism
Minichromosome Maintenance Proteins/metabolism
Multiprotein Complexes
Phosphorylation
Protein Binding
Replication Origin
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_26582917
Owner Institution: FSU
Is Part Of: Nucleic acids research.
1362-4962
Issue: iss. 1, vol. 44

Choose the citation style.
Perez-Arnaiz, P., Bruck, I., & Kaplan, D. L. (2016). Mcm10 coordinates the timely assembly and activation of the replication fork helicase. Nucleic Acids Research. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_26582917