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

Dee R. Denver, Seth Feinberg, Suzanne Estes, W. Kelley Thomas, Michael Lynch

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 ∼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 ∼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.

Original languageEnglish (US)
Pages (from-to)107-113
Number of pages7
JournalGenetics
Volume170
Issue number1
DOIs
StatePublished - May 1 2005
Externally publishedYes

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DNA Mismatch Repair
Caenorhabditis elegans
Mutation Rate
Mutation
Genome
Genomic Instability
Base Pairing
Saccharomyces cerevisiae
Nucleotides
Yeasts
Genotype
Mutation Accumulation

ASJC Scopus subject areas

  • Genetics

Cite this

Mutation rates, spectra and hotspots in mismatch repair-deficient Caenorhabditis elegans. / Denver, Dee R.; Feinberg, Seth; Estes, Suzanne; Thomas, W. Kelley; Lynch, Michael.

In: Genetics, Vol. 170, No. 1, 01.05.2005, p. 107-113.

Research output: Contribution to journalArticle

Denver, Dee R. ; Feinberg, Seth ; Estes, Suzanne ; Thomas, W. Kelley ; Lynch, Michael. / Mutation rates, spectra and hotspots in mismatch repair-deficient Caenorhabditis elegans. In: Genetics. 2005 ; Vol. 170, No. 1. pp. 107-113.
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