Different frameshift mutation spectra in non-repetitive DNA of MutSalpha- and MutLalpha-deficient fission yeast cells

DNA Repair (Amst). 2003 May 13;2(5):571-80. doi: 10.1016/s1568-7864(03)00023-5.

Abstract

A frameshift reversion assay has been established for Schizosaccharomyces pombe, which allows detection of deletions and insertions of nucleotides in a non-repetitive DNA sequence. Compared to wild type, frameshift mutation rates were increased in the mismatch repair (MMR) mutants msh2, msh6, mlh1, and pms1, but not in a swi4 strain (defective in the Msh3 homologue). Rates were also elevated in the DNA nuclease-deficient strains rad2 (defective in the FEN-1 homologue) and exo1. In MutSalpha-deficient strains, msh2 and msh6, most of the reversions were 1bp deletions. In contrast, mlh1 and pms1 mutants, defective in MutLalpha, accumulated significantly more 2bp insertions, preferentially of the type CG to (CG)(2). Such duplications were less frequent in double mutants additionally defective in msh2, msh6, rad2, or exo1. Thus, accumulation of (CG)(2) in MutLalpha-deficient strains depends on the presence of MutSalpha, Rad2 and Exo1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins / genetics*
  • DNA Repair
  • DNA* / ultrastructure*
  • DNA-Binding Proteins / genetics*
  • Deoxyribonucleases / metabolism
  • Endodeoxyribonucleases / genetics
  • Exodeoxyribonucleases / genetics
  • Frameshift Mutation*
  • Fungal Proteins / genetics*
  • Gene Deletion
  • Genotype
  • Models, Genetic
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • Mutation*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces pombe Proteins*
  • Transcription Factors / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • DNA-Binding Proteins
  • Fungal Proteins
  • MLH1 protein, S cerevisiae
  • MSH6 protein, S cerevisiae
  • SWI4 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Schizosaccharomyces pombe Proteins
  • Transcription Factors
  • DNA
  • Deoxyribonucleases
  • Endodeoxyribonucleases
  • Exodeoxyribonucleases
  • exodeoxyribonuclease I
  • Rad2 protein, S pombe
  • MSH2 protein, S cerevisiae
  • MutL Protein Homolog 1
  • MutS Homolog 2 Protein
  • msh2 protein, S pombe