Genomic Instability Induced by Mutations in Saccharomyces cerevisiae POL1

Corresponding author: Teresa S.-F. Wang, Edwards Bldg., Rm. R270, Stanford University Medical Center, 300 Pasteur Dr., Stanford, CA 94305. E-mail address: twang@pmgm2.stanford.edu

Communicating editor: F. WINSTON

Mutations of chromosome replication genes can be one of the early events that promote genomic instability. Among genes that are involved in chromosomal replication, DNA polymerase is essential for initiation of replication and lagging-strand synthesis. Here we examined the effect of two mutations in S. cerevisiae POL1, pol1-1 and pol1-17, on a microsatellite (GT)₁₆ tract. The pol1-17 mutation elevated the mutation rate 13-fold by altering sequences both inside and downstream of the (GT)₁₆ tract, whereas the pol1-1 mutation increased the mutation rate 54-fold by predominantly altering sequences downstream of the (GT)₁₆ tract in a RAD52-dependent manner. In a rad52 null mutant background pol1-1 and pol1-17 also exhibited different plasmid and chromosome loss phenotypes. Deletions of mismatch repair (MMR) genes induce a differential synergistic increase in the mutation rates of pol1-1 and pol1-17. These findings suggest that perturbations of DNA replication in these two pol1 mutants are caused by different mechanisms, resulting in various types of mutations. Thus, mutations of POL1 can induce a variety of mutator phenotypes and can be a source of genomic instability in cells.

This article has been cited by other articles:

				R. M. Ricke and A.-K. Bielinsky A Conserved Hsp10-like Domain in Mcm10 Is Required to Stabilize the Catalytic Subunit of DNA Polymerase-{alpha} in Budding Yeast J. Biol. Chem., July 7, 2006; 281(27): 18414 - 18425. [Abstract] [Full Text] [PDF]

				M. Kai, M. N. Boddy, P. Russell, and T. S.-F. Wang Replication checkpoint kinase Cds1 regulates Mus81 to preserve genome integrity during replication stress Genes & Dev., April 15, 2005; 19(8): 919 - 932. [Abstract] [Full Text] [PDF]

				Y. Zhou and T. S.-F. Wang A Coordinated Temporal Interplay of Nucleosome Reorganization Factor, Sister Chromatin Cohesion Factor, and DNA Polymerase {alpha} Facilitates DNA Replication Mol. Cell. Biol., November 1, 2004; 24(21): 9568 - 9579. [Abstract] [Full Text] [PDF]