Nearby inverted repeats fuse to generate acentric and dicentric palindromic chromosomes by a replication template exchange mechanism (original) (raw)

  1. Ken'Ichi Mizuno1,
  2. Sarah Lambert2,
  3. Giuseppe Baldacci2,
  4. Johanne M. Murray1,4 and
  5. Antony M. Carr1,3
  6. 1Genome Damage and Stability Centre, University of Sussex, Brighton Sussex BN1 9RQ, United Kingdom;
  7. 2Institut Curie-CNRS, UMR2027, Régulation de la réplication des eucaryotes, Université Paris Sud-XI, Bat 110, 91405 Orsay, France

Abstract

Gene amplification plays important roles in the progression of cancer and contributes to acquired drug resistance during treatment. Amplification can initiate via dicentric palindromic chromosome production and subsequent breakage–fusion–bridge cycles. Here we show that, in fission yeast, acentric and dicentric palindromic chromosomes form by homologous recombination protein-dependent fusion of nearby inverted repeats, and that these fusions occur frequently when replication forks arrest within the inverted repeats. Genetic and molecular analyses suggest that these acentric and dicentric palindromic chromosomes arise not by previously described mechanisms, but by a replication template exchange mechanism that does not involve a DNA double-strand break. We thus propose an alternative mechanism for the generation of palindromic chromosomes dependent on replication fork arrest at closely spaced inverted repeats.

Keywords:

Footnotes