ArticleMolecular biology of the cell2008
Interplay between S-cyclin-dependent kinase and Dbf4-dependent kinase in controlling DNA replication through phosphorylation of yeast Mcm4 N-terminal domain.
Article in Molecular biology of the cell, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Regulation of Cell Cycle Entry and Exit: A Single Cell Perspective.Comprehensive Physiology · 2019Review
- Control of Eukaryotic DNA Replication Initiation-Mechanisms to Ensure Smooth Transitions.Genes · 2019Review
- Mechanisms and regulation of DNA replication initiation in eukaryotes.Critical reviews in biochemistry and molecular biology · 2017Review
- Review
- Article
- Characterization of a Novel MMS-Sensitive Allele of Schizosaccharomyces pombe mcm4.G3 (Bethesda, Md.) · 2016Article
- The key role of CYC2 during meiosis in Tetrahymena thermophila.Protein & cell · 2016Article
- Concerted activities of Mcm4, Sld3, and Dbf4 in control of origin activation and DNA replication fork progression.Genome research · 2016Article
- Structural Mechanisms of Hexameric Helicase Loading, Assembly, and Unwinding.F1000Research · 2016Review
- Domain within the helicase subunit Mcm4 integrates multiple kinase signals to control DNA replication initiation and fork progression.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Helicase activation and establishment of replication forks at chromosomal origins of replication.Cold Spring Harbor perspectives in biology · 2013Review
- The Cdc45·Mcm2-7·GINS protein complex in trypanosomes regulates DNA replication and interacts with two Orc1-like proteins in the origin recognition complex.The Journal of biological chemistry · 2011Article
- Review
- Mec1 is one of multiple kinases that prime the Mcm2-7 helicase for phosphorylation by Cdc7.Molecular cell · 2010Article
- Candida albicans cyclin Clb4 carries S-phase cyclin activity.Eukaryotic cell · 2010Article
- How do Cdc7 and cyclin-dependent kinases trigger the initiation of chromosome replication in eukaryotic cells?Genes & development · 2010Review
- Replication origins and timing of temporal replication in budding yeast: how to solve the conundrum?Current genomics · 2010Article
- Article
- Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species.PLoS biology · 2009Article
- Incorporation into the prereplicative complex activates the Mcm2-7 helicase for Cdc7-Dbf4 phosphorylation.Genes & development · 2009Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cyclin-dependent (CDK) and Dbf4-dependent (DDK) kinases trigger DNA replication in all eukaryotes, but how these kinases cooperate to regulate DNA synthesis is largely unknown. Here, we show that budding yeast Mcm4 is phosphorylated in vivo during S phase in a manner dependent on the presence of five CDK phosphoacceptor residues within the N-terminal domain of Mcm4. Mutation to alanine of these five sites (mcm4-5A) abolishes phosphorylation and decreases replication origin firing efficiency at 22 degrees C. Surprisingly, the loss of function mcm4-5A mutation confers cold and hydroxyurea sensitivity to DDK gain of function conditions (mcm5/bob1 mutation or DDK overexpression), implying that phosphorylation of Mcm4 by CDK somehow counteracts negative effects produced by ectopic DDK activation. Deletion of the S phase cyclins Clb5,6 is synthetic lethal with mcm4-5A and mimics its effects on DDK up mutants. Furthermore, we find that Clb5 expressed late in the cell cycle can still suppress the lethality of clb5,6Delta bob1 cells, whereas mitotic cyclins Clb2, 3, or 4 expressed early cannot. We propose that the N-terminal extension of eukaryotic Mcm4 integrates regulatory inputs from S-CDK and DDK, which may play an important role for the proper assembly or stabilization of replisome-progression complexes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.