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Molecular and Cellular Biology, October 2008, p. 5977-5985, Vol. 28, No. 19
0270-7306/08/$08.00+0     doi:10.1128/MCB.00596-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The DNA Replication Checkpoint Directly Regulates MBF-Dependent G1/S Transcription{triangledown}

Chaitali Dutta,1 Prasanta K. Patel,1 Adam Rosebrock,2 Anna Oliva,2 Janet Leatherwood,2 and Nicholas Rhind1*

Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605,1 Department of Molecular Genetics and Microbiology, State University of New York, Stony Brook, New York 117942

Received 11 April 2008/ Returned for modification 13 May 2008/ Accepted 15 July 2008

The DNA replication checkpoint transcriptionally upregulates genes that allow cells to adapt to and survive replication stress. Our results show that, in the fission yeast Schizosaccharomyces pombe, the replication checkpoint regulates the entire G1/S transcriptional program by directly regulating MBF, the G1/S transcription factor. Instead of initiating a checkpoint-specific transcriptional program, the replication checkpoint targets MBF to maintain the normal G1/S transcriptional program during replication stress. We propose a mechanism for this regulation, based on in vitro phosphorylation of the Cdc10 subunit of MBF by the Cds1 replication-checkpoint kinase. Replacement of two potential phosphorylation sites with phosphomimetic amino acids suffices to promote the checkpoint transcriptional program, suggesting that Cds1 phosphorylation directly regulates MBF-dependent transcription. The conservation of MBF between fission and budding yeast, and recent results implicating MBF as a target of the budding yeast replication checkpoint, suggests that checkpoint regulation of the MBF transcription factor is a conserved strategy for coping with replication stress. Furthermore, the structural and regulatory similarity between MBF and E2F, the metazoan G1/S transcription factor, suggests that this checkpoint mechanism may be broadly conserved among eukaryotes.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605. Phone: (508) 856-8316. Fax: (508) 856-6464. E-mail: nick.rhind{at}umassmed.edu

{triangledown} Published ahead of print on 28 July 2008.

Molecular and Cellular Biology, October 2008, p. 5977-5985, Vol. 28, No. 19
0270-7306/08/$08.00+0     doi:10.1128/MCB.00596-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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