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Cdc7 is required throughout the yeast S phase to activate replication origins
A D Donaldson1, W L Fangman, B J Brewer
1Department of Genetics, University of Washington, Seattle, Washington 98195-7360, USA.
Genes & Development
|March 21, 1998
Summary
The Cdc7 kinase is crucial for activating DNA replication origins in Saccharomyces cerevisiae. This study reveals Cdc7 kinase activates early and late origins separately, with late origins needing activity later in S phase.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The Cdc7 kinase in Saccharomyces cerevisiae was previously thought to solely initiate S phase.
- Emerging evidence suggests Cdc7 kinase acts directly on individual replication origins.
Purpose of the Study:
- To investigate differential requirements of early- and late-activated replication origins for Cdc7 kinase activity.
- To elucidate the temporal and quantitative roles of Cdc7 kinase in DNA replication initiation.
Main Methods:
- Utilized a temperature-sensitive cdc7 allele (cdc7(ts)) in Saccharomyces cerevisiae.
- Synchronized cell cycles to G1 arrest and subsequent entry into S phase at different temperatures.
- Assessed replication of early- and late-activated origins and chromosomal sequences.
Main Results:
- Cells with cdc7(ts) mutation failed to activate late replication origins when shifted to restrictive temperature during S phase.
- Replication of sequences normally initiated from late origins was significantly delayed.
- Reducing Cdc7 kinase levels affected early and late origin activation similarly, suggesting temporal rather than quantitative differences.
Conclusions:
- Cdc7 kinase plays distinct roles in the activation of early and late replication origins.
- Late replication origins require Cdc7 kinase activity later in S phase for initiation.
- This finding refines the understanding of S phase regulation and DNA replication control.