Long CTG·CAG repeats from myotonic dystrophy are preferred sites for intermolecular recombination

Anna Pluciennik, Ravi R. Iyer, Marek Napierala, Jacquelynn E. Larson, Marcin Filutowicz, Robert D. Wells

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Homologous recombination was shown to enable the expansion of CTG·CAG repeat sequences. Other prior investigations revealed the involvement of replication and DNA repair in these genetic instabilities. Here we used a genetic assay to measure the frequency of homologous intermolecular recombination between two CTG·CAG tracts. When compared with non-repeating sequences of similar lengths, long (CTG·CAG)n repeats apparently recombine with an ∼60-fold higher frequency. Sequence polymorphisms that interrupt the homogeneity of the CTG·CAG repeat tracts reduce the apparent recombination frequency as compared with the pure uninterrupted repeats. The orientation of the repeats relative to the origin of replication strongly influenced the apparent frequency of recombination. This suggests the involvement of DNA replication in the recombination process of triplet repeats. We propose that DNA polymerases stall within the CTG·CAG repeat tracts causing nicks or double-strand breaks that stimulate homologous recombination. The recombination process is RecA-dependent.

Original languageEnglish (US)
Pages (from-to)34074-34086
Number of pages13
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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