Variation in efficiency of DNA mismatch repair at different sites in the yeast genome

Evolutionary studies have suggested that mutation rates vary significantly at different positions in the eukaryotic genome. The mechanism that is responsible for this context-dependence of mutation rates is not understood. We demonstrate experimentally that frameshift mutation rates in yeast microsa...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-06, Vol.102 (24), p.8639-8643
Main Authors: Hawk, J.D, Stefanovic, L, Boyer, J.C, Petes, T.D, Farber, R.A
Format: Article
Language:English
Subjects:
Base Pair Mismatch - genetics
Base Sequence
Biological Sciences
chromatin
chromatin structure
Chromosomes
DNA
DNA mismatch repair
DNA Primers
DNA repair
DNA Repair - physiology
Eukaryotes
frameshift mutation
Frameshift Mutation - genetics
Fungal Proteins - genetics
Genes
Genes, Reporter - genetics
Genetic mutation
Genetics
genome
Genome, Fungal
Genomes
Genomics
Medical genetics
microsatellite repeats
Microsatellite Repeats - genetics
Microsatellites
Mutation
Polymerase chain reaction
Reporter genes
Saccharomyces cerevisiae
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - physiology
Yeast
Yeasts
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Evolutionary studies have suggested that mutation rates vary significantly at different positions in the eukaryotic genome. The mechanism that is responsible for this context-dependence of mutation rates is not understood. We demonstrate experimentally that frameshift mutation rates in yeast microsatellites depend on the genomic context and that this variation primarily reflects the context-dependence of the efficiency of DNA mismatch repair. We measured the stability of a 16.5-repeat polyGT tract by using a reporter gene (URA3-GT) in which the microsatellite was inserted in-frame into the yeast URA3 gene. We constructed 10 isogenic yeast strains with the reporter gene at different locations in the genome. Rates of frameshift mutations that abolished the correct reading frame of this gene were determined by fluctuation analysis. A 16-fold difference was found among these strains. We made mismatch-repair-deficient (msh2) derivatives of six of the strains. Mutation rates were elevated for all of these strains, but the differences in rates among the strains were substantially reduced. The simplest interpretation of this result is that the efficiency of DNA mismatch repair varies in different regions of the genome, perhaps reflecting some aspect of chromosome structure.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0503415102