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Phosphorylation of Mcm2 by Cdc7 promotes pre-replication complex assembly during cell-cycle re-entry
Li-Chiou Chuang1, Leonardo K Teixeira, James A Wohlschlegel
1Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Molecular Cell
|August 4, 2009
Summary
Cyclin E, via Cdk2 activation, promotes DNA replication by enhancing Mcm2 loading. This involves increasing Cdc7 levels, crucial for pre-replication complex assembly during cell cycle re-entry from quiescence.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cell cycle re-entry from quiescence requires pre-replication complex (Pre-RC) assembly.
- Pre-RC assembly involves loading of Mcm2-7 subunits, a critical step for DNA replication initiation.
Purpose of the Study:
- To investigate the role of Cyclin E in Pre-RC assembly during cell cycle re-entry.
- To elucidate the molecular mechanisms by which Cyclin E influences Mcm2 loading onto chromatin.
Main Methods:
- Cell-based assays examining protein and mRNA levels.
- Chromatin loading assays.
- Analysis of phosphomimetic mutants and ectopic gene expression.
Main Results:
- Cyclin E, through Cdk2 activation, promotes Mcm2 loading onto chromatin.
- This process is partly mediated by increased Cdc7 accumulation (mRNA and protein).
- A phosphomimetic Mcm2 mutant bypasses the need for Cdc7 in Mcm2 loading; ectopic Cdc6/Cdc7 rescues Cdk2-inhibited MCM loading.
Conclusions:
- Cyclin E-Cdk2 signaling is essential for promoting Cdc6 and Cdc7 accumulation.
- This accumulation is required for Mcm2 loading during cell cycle re-entry from quiescence.
- Highlights a key regulatory pathway for initiating DNA replication.
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Two states at the origin of replication
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In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
02:38S-Cdk Initiates DNA Replication
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of replication.
Two states at the origin of replication
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