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Eukaryotic Cell, January 2005, p. 166-177, Vol. 4, No. 1
1535-9778/05/$08.00+0     doi:10.1128/EC.4.1.166-177.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Mcl1p Is a Polymerase {alpha} Replication Accessory Factor Important for S-Phase DNA Damage Survival

Dewight R. Williams* and J. R. McIntosh

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado

Received 15 June 2004/ Accepted 26 October 2004

Mcl1p is an essential fission yeast chromatin-binding protein that belongs to a family of highly conserved eukaryotic proteins important for sister chromatid cohesion. The essential function is believed to result from its role as a Pol1p (polymerase {alpha}) accessory protein, a conclusion based primarily on analogy to Ctf4p's interaction with Pol1p. In this study, we show that Mcl1p also binds to Pol1p with high affinity for the N terminus of Pol1p during S phase and DNA damage. Characterization of an inducible allele of mcl1+, nmt41mcl1-MH, shows that altered expression levels of Mcl1p lead to sensitivity to DNA-damaging agents and synthetic lethality with the replication checkpoint mutations rad3{Delta}, rqh1{Delta}, and hsk1-1312. Further, we find that the overexpression of the S-phase checkpoint kinase, Cds1, or the loss of Hsk1 kinase activity can disrupt Mcl1p's interaction with chromatin and Pol1p during replication arrest with hydroxyurea. We take these data to mean that Mcl1p is a dynamic component of the polymerase {alpha} complex during replication and is important for the replication stress response in fission yeast.

* Corresponding author. Present address: Molecular Physiology and Biophysics, 710 Light Hall, Vanderbilt University-Medical Center, Nashville, TN 37232-8725. Phone: (615) 322-7898. Fax: (615) 322-7236. E-mail: Dewight.williams{at}vanderbilt.edu.

Eukaryotic Cell, January 2005, p. 166-177, Vol. 4, No. 1
1535-9778/05/$08.00+0     doi:10.1128/EC.4.1.166-177.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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