Long CTG·CAG repeat sequences markedly stimulate intramolecular recombination

Marek Napierala, Pawel Parniewski, Anna Pluciennik, Robert D. Wells

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Previous studies have shown that homologous recombination is a powerful mechanism for generation of massive instabilities of the myotonic dystrophy CTG·CAG sequences. However, the frequency of recombination between the CTG·CAG tracts has not been studied. Here we performed a systematic study on the frequency of recombination between these sequences using a genetic assay based on an intramolecular plasmid system in Escherichia coli. The rate of intramolecular recombination between long CTG·CAG tracts oriented as direct repeats was extraordinarily high; recombinants were found with a frequency exceeding 12%. Recombination occurred in both RecA+ and RecA- cells but was ∼2-11 times higher in the recombination proficient strain. Long CTG·CAG tracts recombined ∼10 times more efficiently than non-repeating control sequences of similar length. The recombination frequency was 60-fold higher for a pair of (CTG·CAG)165 tracts compared with a pair of (CTG·CAG)17 sequences. The CTG·CAG sequences in orientation II (CTG repeats present on a lagging strand template) recombine ∼2-4 times more efficiently than tracts of identical length in the opposite orientation relative to the origin of replication. This orientation effect implies the involvement of DNA replication in the intramolecular recombination between CTG·CAG sequences. Thus, long CTG·CAG tracts are hot spots for genetic recombination.

Original languageEnglish (US)
Pages (from-to)34087-34100
Number of pages14
JournalJournal of Biological Chemistry
Volume277
Issue number37
DOIs
StatePublished - Sep 13 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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