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Vol. 18, Issue 10, 3894-3902, October 2007
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*Cancer Research U.K., Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, United Kingdom; and Cancer Research Institute, Fundación Investigación del Cáncer-Universidad de Salamanca/Consejo Superior de Investigaciones Cientificas, 37007 Salamanca, Spain
Submitted May 25, 2007;
Revised July 9, 2007;
Accepted July 13, 2007
Monitoring Editor: Karsten Weis
The Mrc1 and Tof1 proteins are conserved throughout evolution, and in budding yeast they are known to associate with the MCM helicase and regulate the progression of DNA replication forks. Previous work has shown that Mrc1 is important for the activation of checkpoint kinases in responses to defects in S phase, but both Mrc1 and Tof1 also regulate the normal process of chromosome replication. Here, we show that these two important factors control the normal progression of DNA replication forks in distinct ways. The rate of progression of DNA replication forks is greatly reduced in the absence of Mrc1 but much less affected by loss of Tof1. In contrast, Tof1 is critical for DNA replication forks to pause at diverse chromosomal sites where nonnucleosomal proteins bind very tightly to DNA, and this role is not shared with Mrc1.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
These authors contributed equally to this work.
Address correspondence to: Karim Labib (klabib{at}picr.man.ac.uk)
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