Genetics. Published Articles Ahead of Print: October 11, 2005, Copyright © 2005
doi:10.1534/genetics.105.049254


A more recent version of this article appeared on January 1, 2006.

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DNA Polymerase 4 of Saccharomyces Cerevisae is Important for Accurate Repair of MMS-Induced DNA Damage

Catherine H. Sterling 1 and Joann B. Sweasy 1*

1 Yale University School of Medicine

* To whom correspondence should be addressed. E-mail: joann.sweasy{at}yale.edu.

Submitted on August 5, 2005
Revised on September 15, 2005
Accepted on 7 October 2005


Abstract

The DNA polymerase 4 protein (Pol4) of Saccharomyces cerevisiae is a member of the X family of DNA polymerases whose closest human relative appears to be DNA polymerase lambda. Results from previous genetic studies conflict over the role of Pol 4 in vivo. Here we show that deletion of Pol 4 in a diploid strain of the SK1 genetic background results in sensitivity to methylmethanesulfonate (MMS). However, deletion of Pol 4 in other strain backgrounds and in haploid strains does not yield an observable phenotype. The MMS sensitivity of a Pol4-deficient strain can be rescued by deletion of YKu70. We also show that deletion of Pol 4 results in a 6-14-fold increase in the MMS-induced mutation frequency and in a significant increase in AT to TA transversions. Our studies suggest that Pol 4 is critical for accurate repair of DNA lesions induced by MMS.

Key Words: Base excision repair, DNA polymerase 4, DNA polymerase beta, DNA polymerase lambda, non-homologous end joing