DNA replication checkpoint promotes G1-S transcription by inactivating the MBF repressor Nrm1
- R. A. M. de Bruin*,
- T. I. Kalashnikova*,
- A. Aslanian†,‡,
- J. Wohlschlegel†,§,
- C. Chahwan*,¶,
- J. R. Yates III†,
- P. Russell*,†, and
- C. Wittenberg*,†,‖
- Departments of *Molecular Biology and
- †Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and
- ‡Molecular and Cellular Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099
-
Edited by John B. Gurdon, University of Cambridge, Cambridge, United Kingdom, and approved June 3, 2008 (received for review February 3, 2008)
Abstract
The cell cycle transcriptional program imposes order on events of the cell-cycle and is a target for signals that regulate cell-cycle progression, including checkpoints required to maintain genome integrity. Neither the mechanism nor functional significance of checkpoint regulation of the cell-cycle transcription program are established. We show that Nrm1, an MBF-specific transcriptional repressor acting at the transition from G1 to S phase of the cell cycle, is at the nexus between the cell cycle transcriptional program and the DNA replication checkpoint in fission yeast. Phosphorylation of Nrm1 by the Cds1 (Chk2) checkpoint protein kinase, which is activated in response to DNA replication stress, promotes its dissociation from the MBF transcription factor. This leads to the expression of genes encoding components that function in DNA replication and repair pathways important for cell survival in response to arrested DNA replication.
Footnotes
- ‖To whom correspondence should be addressed. E-mail: curtw{at}scripps.edu
-
Author contributions: R.A.M.d.B., C.C., P.R., and C.W. designed research; R.A.M.d.B. and T.I.K. performed research; A.A., J.W., and J.R.Y. contributed new reagents/analytic tools; R.A.M.d.B., P.R., and C.W. analyzed data; and R.A.M.d.B. and C.W. wrote the paper.
-
↵ §Present address: Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA, 90095-1737.
-
↵ ¶Present address: Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
-
The authors declare no conflict of interest.
-
This article is a PNAS Direct Submission.
- © 2008 by The National Academy of Sciences of the USA
