Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression

Sheu, Y. J., Stillman, B. (2006) Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression. Mol Cell, 24 (1). pp. 101-13. ISSN 1097-2765 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/17018296
DOI: 10.1016/j.molcel.2006.07.033

Abstract

Origins of DNA replication are licensed in G1 by recruiting the minichromosome maintenance (MCM) proteins to form a prereplicative complex (pre-RC). Prior to initiation of DNA synthesis from each origin, a preinitiation complex (pre-IC) containing Cdc45 and other proteins is formed. We report that Cdc7-Dbf4 protein kinase (DDK) promotes assembly of a stable Cdc45-MCM complex exclusively on chromatin in S phase. In this complex, Mcm4 is hyperphosphorylated. Studies in vitro using purified DDK and Mcm4 demonstrate that hyperphosphorylation occurs at the Mcm4 N terminus. However, the DDK substrate specificity is conferred by an adjacent DDK-docking domain (DDD), sufficient for facilitating efficient phosphorylation of artificial phosphoacceptors in cis. Genetic evidence suggests that phosphorylation of Mcm4 by DDK is important for timely S phase progression and for cell viability upon overproduction of Cdc45. We suggest that DDK docks on and phosphorylates MCM proteins at licensed origins to promote proper assembly of pre-IC.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Motifs Apoenzymes metabolism Binding Sites Cell Cycle Proteins chemistry metabolism/physiology Chromatin metabolism Conserved Sequence DNA Replication DNA-Binding Proteins chemistry metabolism physiology Models Biological Molecular Sequence Data Nuclear Proteins chemistry metabolism physiology Phosphorylation Protein Structure Tertiary Protein-Serine-Threonine Kinases chemistry metabolism physiology S Phase physiology Saccharomyces cerevisiae cytology genetics metabolism Saccharomyces cerevisiae Proteins chemistry metabolism/physiology Sequence Alignment
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > minichromosome maintenance proteins
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: CSHL Librarian
Date Deposited: 09 Dec 2011 16:10
Last Modified: 20 Jun 2017 16:46
PMCID: PMC2923825
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22899

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