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Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12765-70. doi: 10.1073/pnas.0904623106. Epub 2009 Jun 10.

Mrc1 phosphorylation in response to DNA replication stress is required for Mec1 accumulation at the stalled fork.

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1
Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women's Hospital, Howard Hughes Medical Institute, Boston, MA 02115, USA.

Abstract

DNA replication stress activates a response pathway that stabilizes stalled forks and promotes the completion of replication. The budding yeast Mec1 sensor kinase, Mrc1 mediator, and Rad53 effector kinase are central to this signal transduction cascade in S phase. We report that Mec1-dependent, Rad53-independent phosphorylation of Mrc1 is required to establish a positive feedback loop that stabilizes Mec1 and the replisome at stalled forks. A structure-function analysis of Mrc1 also uncovered a central region required for proper mediator function and association with replisome components. Together these results reveal new insight into how Mrc1 facilitates checkpoint signal amplification at stalled replication forks.

PMID:
19515819
PMCID:
PMC2722297
DOI:
10.1073/pnas.0904623106
[Indexed for MEDLINE]
Free PMC Article
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