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Conserved mechanism for coordinating replication fork helicase assembly with phosphorylation of the helicase.

Title: Conserved mechanism for coordinating replication fork helicase assembly with phosphorylation of the helicase.
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Name(s): Bruck, Irina, author
Kaplan, Daniel L, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2015-09-08
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Dbf4-dependent kinase (DDK) phosphorylates minichromosome maintenance 2 (Mcm2) during S phase in yeast, and Sld3 recruits cell division cycle 45 (Cdc45) to minichromosome maintenance 2-7 (Mcm2-7). We show here DDK-phosphoryled Mcm2 preferentially interacts with Cdc45 in vivo, and that Sld3 stimulates DDK phosphorylation of Mcm2 by 11-fold. We identified a mutation of the replication initiation factor Sld3, Sld3-m16, that is specifically defective in stimulating DDK phosphorylation of Mcm2. Wild-type expression levels of sld3-m16 result in severe growth and DNA replication defects. Cells expressing sld3-m16 exhibit no detectable Mcm2 phosphorylation in vivo, reduced replication protein A-ChIP signal at an origin, and diminished Go, Ichi, Ni, and San association with Mcm2-7. Treslin, the human homolog of Sld3, stimulates human DDK phosphorylation of human Mcm2 by 15-fold. DDK phosphorylation of human Mcm2 decreases the affinity of Mcm5 for Mcm2, suggesting a potential mechanism for helicase ring opening. These data suggest a conserved mechanism for replication initiation: Sld3/Treslin coordinates Cdc45 recruitment to Mcm2-7 with DDK phosphorylation of Mcm2 during S phase.
Identifier: FSU_pmch_26305950 (IID), 10.1073/pnas.1509608112 (DOI), PMC4568703 (PMCID), 26305950 (RID), 26305950 (EID), 1509608112 (PII)
Keywords: DNA replication, Helicase, Initiation, Kinase, Phosphorylation
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568703.
Subject(s): Blotting, Western
Cell Cycle Proteins/genetics
Cell Cycle Proteins/metabolism
DNA Replication
DNA-Binding Proteins/genetics
DNA-Binding Proteins/metabolism
Humans
Minichromosome Maintenance Complex Component 2/genetics
Minichromosome Maintenance Complex Component 2/metabolism
Minichromosome Maintenance Proteins/genetics
Minichromosome Maintenance Proteins/metabolism
Mutation
Nuclear Proteins/genetics
Nuclear Proteins/metabolism
Phosphorylation
Protein Binding
Protein-Serine-Threonine Kinases/genetics
Protein-Serine-Threonine Kinases/metabolism
Saccharomyces cerevisiae/genetics
Saccharomyces cerevisiae/growth & development
Saccharomyces cerevisiae/metabolism
Saccharomyces cerevisiae Proteins/genetics
Saccharomyces cerevisiae Proteins/metabolism
Signal Transduction/genetics
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_26305950
Owner Institution: FSU
Is Part Of: Proceedings of the National Academy of Sciences of the United States of America.
1091-6490
Issue: iss. 36, vol. 112

Choose the citation style.
Bruck, I., & Kaplan, D. L. (2015). Conserved mechanism for coordinating replication fork helicase assembly with phosphorylation of the helicase. Proceedings Of The National Academy Of Sciences Of The United States Of America. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_26305950