Originally published as Genetics Published Articles Ahead of Print on October 11, 2005.

Genetics, Vol. 172, 89-98, January 2006, Copyright © 2006
doi:10.1534/genetics.105.049254

DNA Polymerase 4 of Saccharomyces cerevisiae Is Important for Accurate Repair of Methyl-Methanesulfonate-Induced DNA Damage

Catherine H. Sterling and Joann B. Sweasy1

Departments of Therapeutic Radiology and Genetics, Yale University, New Haven, Connecticut 06510

1 Corresponding author: Department of Therapeutic Radiology, Yale University School of Medicine, 333 Cedar St., P.O. Box 208040, New Haven, CT 06520.
E-mail: joann.sweasy{at}yale.edu

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 Pol4 in vivo. Here we show that deletion of Pol4 in a diploid strain of the SK1 genetic background results in sensitivity to methyl methanesulfonate (MMS). However, deletion of Pol4 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 Pol4 results in a 6- to 14-fold increase in the MMS-induced mutation frequency and in a significant increase in AT-to-TA transversions. Our studies suggest that Pol4 is critical for accurate repair of DNA lesions induced by MMS.