Mutation rates, spectra and hotspots in mismatch repair-deficient Caenorhabditis elegans.

Academic Article

Abstract

  • Although it is clear that postreplicative DNA mismatch repair (MMR) plays a critical role in maintaining genomic stability in nearly all forms of life surveyed, much remains to be understood about the genome-wide impact of MMR on spontaneous mutation processes and the extent to which MMR-deficient mutation patterns vary among species. We analyzed spontaneous mutation processes across multiple genomic regions using two sets of mismatch repair-deficient (msh-2 and msh-6) Caenorhabditis elegans mutation-accumulation (MA) lines and compared our observations to mutation spectra in a set of wild-type (WT), repair-proficient C. elegans MA lines. Across most sequences surveyed in the MMR-deficient MA lines, mutation rates were approximately 100-fold higher than rates in the WT MA lines, although homopolymeric nucleotide-run (HP) loci composed of A:T base pairs mutated at an approximately 500-fold greater rate. In contrast to yeast and humans where mutation spectra vary substantially with respect to different specific MMR-deficient genotypes, mutation rates and patterns were overall highly similar between the msh-2 and msh-6 C. elegans MA lines. This, along with the apparent absence of a Saccharomyces cerevisiae MSH3 ortholog in the C. elegans genome, suggests that C. elegans MMR surveillance is carried out by a single Msh-2/Msh-6 heterodimer.
  • Authors

  • Denver, Dee R
  • Feinberg, Seth
  • Estes, Suzanne
  • Thomas, William
  • Lynch, Michael
  • Status

    Publication Date

  • May 2005
  • Published In

  • Genetics  Journal
  • Keywords

  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • DNA Repair
  • DNA-Binding Proteins
  • Genotype
  • Molecular Sequence Data
  • MutS DNA Mismatch-Binding Protein
  • Mutation
  • Digital Object Identifier (doi)

    Start Page

  • 107
  • End Page

  • 113
  • Volume

  • 170
  • Issue

  • 1