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The DNA replication checkpoint directly regulates MBF-dependent G1/S transcription
Chaitali Dutta1, Prasanta K Patel, Adam Rosebrock
1Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Molecular and Cellular Biology
|July 30, 2008
Summary
The DNA replication checkpoint maintains normal G(1)/S gene expression during stress by directly regulating the MBF transcription factor. This conserved mechanism, involving Cds1 kinase phosphorylation, ensures cell survival and adaptation.
Area of Science:
- Cellular biology
- Molecular genetics
- Biochemistry
Background:
- The DNA replication checkpoint is crucial for cellular adaptation and survival under replication stress.
- This checkpoint typically upregulates specific genes to manage replication errors.
Purpose of the Study:
- To investigate how the DNA replication checkpoint regulates transcription in fission yeast (Schizosaccharomyces pombe).
- To determine if the checkpoint initiates a new transcriptional program or modifies an existing one.
Main Methods:
- Investigated the role of the MBF transcription factor in the fission yeast replication checkpoint.
- Performed in vitro phosphorylation assays using the Cds1 kinase and the Cdc10 subunit of MBF.
- Utilized phosphomimetic mutations to assess the functional impact of phosphorylation.
Main Results:
- The replication checkpoint directly regulates MBF, the G(1)/S transcription factor, in Schizosaccharomyces pombe.
- The checkpoint maintains the normal G(1)/S transcriptional program during replication stress, rather than initiating a distinct program.
- Cds1 kinase-mediated phosphorylation of the Cdc10 subunit of MBF directly regulates MBF-dependent transcription.
Conclusions:
- Checkpoint regulation of the MBF transcription factor is a conserved strategy for coping with replication stress.
- This mechanism, involving Cds1 phosphorylation of MBF, is likely conserved across eukaryotes, including metazoans via E2F similarity.
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