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Sequence composition and context effects on the generation and repair of frameshift intermediates in mononucleotide runs in Saccharomyces cerevisiae.

Publication ,  Journal Article
Harfe, BD; Jinks-Robertson, S
Published in: Genetics
October 2000

DNA polymerase slippage occurs frequently in tracts of a tandemly repeated nucleotide, and such slippage events can be genetically detected as frameshift mutations. In long mononucleotide runs, most frameshift intermediates are repaired by the postreplicative mismatch repair (MMR) machinery, rather than by the exonucleolytic proofreading activity of DNA polymerase. Although mononucleotide runs are hotspots for polymerase slippage events, it is not known whether the composition of a run and the surrounding context affect the frequency of slippage or the efficiency of MMR. To address these issues, 10-nucleotide (10N) runs were inserted into the yeast LYS2 gene to create +1 frameshift alleles. Slippage events within these runs were detected as Lys(+) revertants. 10G or 10C runs were found to be more unstable than 10A or 10T runs, but neither the frequency of polymerase slippage nor the overall efficiency of MMR was greatly influenced by sequence context. Although complete elimination of MMR activity (msh2 mutants) affected all runs similarly, analyses of reversion rates in msh3 and msh6 mutants revealed distinct specificities of the yeast Msh2p-Msh3p and Msh2p-Msh6p mismatch binding complexes in the repair of frameshift intermediates in different sequence contexts.

Duke Scholars

Published In

Genetics

DOI

ISSN

0016-6731

Publication Date

October 2000

Volume

156

Issue

2

Start / End Page

571 / 578

Location

United States

Related Subject Headings

  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Protein Subunits
  • Mutation
  • Mutagenesis, Site-Directed
  • MutS Homolog 2 Protein
  • Molecular Sequence Data
  • L-Aminoadipate-Semialdehyde Dehydrogenase
  • Fungal Proteins
  • Frameshift Mutation
 

Citation

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Harfe, B. D., & Jinks-Robertson, S. (2000). Sequence composition and context effects on the generation and repair of frameshift intermediates in mononucleotide runs in Saccharomyces cerevisiae. Genetics, 156(2), 571–578. https://doi.org/10.1093/genetics/156.2.571
Harfe, B. D., and S. Jinks-Robertson. “Sequence composition and context effects on the generation and repair of frameshift intermediates in mononucleotide runs in Saccharomyces cerevisiae.Genetics 156, no. 2 (October 2000): 571–78. https://doi.org/10.1093/genetics/156.2.571.
Harfe, B. D., and S. Jinks-Robertson. “Sequence composition and context effects on the generation and repair of frameshift intermediates in mononucleotide runs in Saccharomyces cerevisiae.Genetics, vol. 156, no. 2, Oct. 2000, pp. 571–78. Pubmed, doi:10.1093/genetics/156.2.571.

Published In

Genetics

DOI

ISSN

0016-6731

Publication Date

October 2000

Volume

156

Issue

2

Start / End Page

571 / 578

Location

United States

Related Subject Headings

  • Saccharomyces cerevisiae Proteins
  • Saccharomyces cerevisiae
  • Protein Subunits
  • Mutation
  • Mutagenesis, Site-Directed
  • MutS Homolog 2 Protein
  • Molecular Sequence Data
  • L-Aminoadipate-Semialdehyde Dehydrogenase
  • Fungal Proteins
  • Frameshift Mutation