Genetic recombination destabilizes (CTG)n·(CAG) n repeats in E. coli

Vera Hashem, William A. Rosche, Richard R. Sinden

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The expansion of trinucleotide repeats has been implicated in 17 neurological diseases to date. Factors leading to the instability of trinucleotide repeat sequences have thus been an area of intense interest. Certain genes involved in mismatch repair, recombination, nucleotide excision repair, and replication influence the instability of trinucleotide repeats in both Escherichia coli and yeast. Using a genetic assay for repeat deletion in E. coli, the effect of mutations in the recA, recB, and lexA genes on the rate of deletion of (CTG)n·(CAG)n repeats of varying lengths were examined. The results indicate that mutations in recA and recB, which decrease the rate of recombination, had a stabilizing effect on (CAG) n·(CTG)n repeats decreasing the high rates of deletion seen in recombination proficient cells. Thus, recombination proficiency correlates with high rates of genetic instability in triplet repeats. Induction of the SOS system, however, did not appear to play a significant role in repeat instability, nor did the presence of triplet repeats in cells turn on the SOS response. A model is suggested where deletion during exponential growth may result from attempts to restart replication when paused at triplet repeats.

Original languageEnglish (US)
Pages (from-to)95-109
Number of pages15
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume554
Issue number1-2
DOIs
StatePublished - Oct 4 2004

Keywords

  • Recombination
  • Repeat instability
  • Replication restart
  • Template slippage
  • Triplet repeats
  • recA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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