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Published October 10, 2008 | public
Journal Article

Mrc1 and DNA polymerase epsilon function together in linking DNA replication and the S phase checkpoint


Yeast Mrc1, ortholog of metazoan Claspin, is both a central component of normal DNA replication forks and a mediator of the S phase checkpoint. We report that Mrc1 interacts with Pol2, the catalytic subunit of DNA polymerase Є, essential for leading-strand DNA replication and for the checkpoint. In unperturbed cells, Mrc1 interacts independently with both the N-terminal and C-terminal halves of Pol2 (Pol2N and Pol2C). Strikingly, phosphorylation of Mrc1 during the S phase checkpoint abolishes Pol2N binding, but not Pol2C interaction. Mrc1 is required to stabilize Pol2 at replication forks stalled in HILI. The bimodal Mrc1/Pol2 interaction may be an additional step in regulating the S phase checkpoint response to DNA damage on the leading strand. We propose that Mrc1, which also interacts with the MCMs, may modulate coupling of polymerization and unwinding at the replication fork.

Additional Information

© 2008 Elsevier B.V. Received: January 10, 2008. Revised: June 6, 2008. Accepted: August 18, 2008. Published: October 9, 2008. We thank Stephen Elledge and Oscar Aparicio for strains. This work is dedicated to a gifted teacher, Ernest Russ. This work was supported by MEXT Japan, Grant-in-Aid for Scientific Research on Priority Areas, ''Chromosome Cycle,'' to K.S. and M.K.; GCOE program from MEXT Japan to Y.K.; a California Institute for Regenerative Medicine fellowship to H.L.; and National Institutes of Health (NIH) GM25508 and NIH GM087666 to J.L.C.

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