Double-strand break repair can lead to high frequencies of deletions within short CAG/CTG trinucleotide repeats

Mol Gen Genet. 1999 Jun;261(4-5):871-82. doi: 10.1007/s004380050031.


Trinucleotide repeats undergo contractions and expansions in humans, leading in some cases to fatal neurological disorders. The mechanism responsible for these large size variations is unknown, but replication-slippage events are often suggested as a possible source of instability. We constructed a genetic screen that allowed us to detect spontaneous expansions/contractions of a short trinucleotide repeat in yeast. We show that deletion of RAD27, a gene involved in the processing of Okazaki fragments, increases the frequency of contractions tenfold. Repair of a chromosomal double-strand break (DSB) using a trinucleotide repeat-containing template induces rearrangements of the repeat with a frequency 60 times higher than the natural rate of instability of the same repeat. Our data suggest that both gene conversion and single-strand annealing are major sources of trinucleotide repeat rearrangements.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • Checkpoint Kinase 1
  • DNA Damage*
  • DNA Repair*
  • DNA, Fungal / chemistry
  • DNA, Fungal / genetics
  • Gene Conversion
  • Genotype
  • Models, Genetic
  • Mutagenesis
  • Nucleic Acid Conformation
  • Protein Kinases / genetics*
  • Recombination, Genetic
  • Saccharomyces cerevisiae / genetics*
  • Sequence Deletion*
  • Templates, Genetic
  • Trinucleotide Repeats*


  • DNA, Fungal
  • Protein Kinases
  • CHEK1 protein, human
  • Checkpoint Kinase 1