Persistent initiation of DNA replication and chromatin-bound MCM proteins during the cell cycle in cdc6 mutants

Liang, C., Stillman, B. (December 1997) Persistent initiation of DNA replication and chromatin-bound MCM proteins during the cell cycle in cdc6 mutants. Genes and Development, 11 (24). pp. 3375-86. ISSN 08909369 (ISSN)

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DOI: 10.1101/gad.11.24.3375


Faithful inheritance of genetic information requires that DNA be copied only once each cell cycle. Initiation of DNA replication involves the establishment of a prereplication complex (pre-RC) and subsequent activation by CDK/cyclins, converting the pre-RC to a post-RC. The origin recognition complex (ORC), Cdc6p, and the MCM proteins are required for establishing the pre-RC. We show that all six ORC subunits remain bound to chromatin throughout the cell cycle, whereas the MCM proteins cycle on and off, corresponding precisely to transitions of the RC. A newly isolated cdc6 mutant displays promiscuous initiation of DNA replication, increased nuclear DNA content, and constant MCM protein association with chromatin throughout the cell cycle. This gain-of-function cdc6 mutant ignores the negative controls imposed normally on initiation by the CDK/cyclins, suggesting that Cdc6p is a key mediator of once-per-cell-cycle control of DNA replication.

Item Type: Paper
Uncontrolled Keywords: CDC28 Protein Kinase S cerevisiae metabolism Cell Cycle genetics Cell Cycle Proteins genetics/ metabolism Chromatin metabolism DNA Replication Fungal Proteins genetics/metabolism Mutation Replication Origin Saccharomyces cerevisiae/genetics Saccharomyces cerevisiae Proteins Temperature
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
CSHL Authors:
Communities: CSHL labs > Stillman lab
Highlight: Stillman, Bruce W.
Depositing User: CSHL Librarian
Date: 15 December 1997
Date Deposited: 06 Mar 2012 15:05
Last Modified: 20 Jun 2017 19:32
PMCID: PMC316796
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