Fusion of nearby inverted repeats by a replication-based mechanism leads to formation of dicentric and acentric chromosomes that cause genome instability in budding yeast

Andrew L. Paek, Salma Kaochar, Hope Jones, Aly Elezaby, Lisa Shanks, Ted Weinert

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Large-scale changes (gross chromosomal rearrangements [GCRs]) are common in genomes, and are often associated with pathological disorders. We report here that a specific pair of nearby inverted repeats in budding yeast fuse to form a dicentric chromosome intermediate, which then rearranges to form a translocation and other GCRs. We next show that fusion of nearby inverted repeats is general; we found that many nearby inverted repeats that are present in the yeast genome also fuse, as does a pair of synthetically constructed inverted repeats. Fusion occurs between inverted repeats that are separated by several kilobases of DNA and share >20 base pairs of homology. Finally, we show that fusion of inverted repeats, surprisingly, does not require genes involved in double-strand break (DSB) repair or genes involved in other repeat recombination events.We therefore propose that fusion may occur by a DSB-independent, DNA replication-based mechanism (which we term "faulty template switching"). Fusion of nearby inverted repeats to form dicentrics may be a major cause of instability in yeast and in other organisms.

Original languageEnglish (US)
Pages (from-to)2861-2875
Number of pages15
JournalGenes and Development
Volume23
Issue number24
DOIs
StatePublished - Dec 15 2009

Keywords

  • Acentric and dicentric chromosomes
  • Breakage-fusion-bridge cycle
  • Genome instability
  • Inverted repeats
  • Large palindromes
  • Template switch

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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