Identification of a mutant DNA polymerase delta in Saccharomyces cerevisiae with an antimutator phenotype for frameshift mutations.

Published

Journal Article

We propose that a beta-turn-beta structure, which plays a critical role in exonucleolytic proofreading in the bacteriophage T4 DNA polymerase, is also present in the Saccharomyces cerevisiae DNA pol delta. Site-directed mutagenesis was used to test this proposal by introducing a mutation into the yeast POL3 gene in the region that encodes the putative beta-turn-beta structure. The mutant DNA pol delta has a serine substitution in place of glycine at position 447. DNA replication fidelity of the G447S-DNA pol delta was determined in vivo by using reversion and forward assays. An antimutator phenotype for frameshift mutations in short homopolymeric tracts was observed for the G447S-DNA pol delta in the absence of postreplication mismatch repair, which was produced by inactivation of the MSH2 gene. Because the G447S substitution reduced frameshift but not base substitution mutagenesis, some aspect of DNA polymerase proofreading appears to contribute to production of frameshifts. Possible roles of DNA polymerase proofreading in frameshift mutagenesis are discussed.

Full Text

Duke Authors

Cited Authors

  • Hadjimarcou, MI; Kokoska, RJ; Petes, TD; Reha-Krantz, LJ

Published Date

  • May 2001

Published In

Volume / Issue

  • 158 / 1

Start / End Page

  • 177 - 186

PubMed ID

  • 11333228

Pubmed Central ID

  • 11333228

International Standard Serial Number (ISSN)

  • 0016-6731

Language

  • eng

Conference Location

  • United States