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 language | English (US) |
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Pages (from-to) | 2861-2875 |
Number of pages | 15 |
Journal | Genes and Development |
Volume | 23 |
Issue number | 24 |
DOIs | |
State | Published - 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