Journal
GENES & DEVELOPMENT
Volume 23, Issue 24, Pages 2861-2875Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1862709
Keywords
Inverted repeats; acentric and dicentric chromosomes; breakage-fusion-bridge cycle; genome instability; large palindromes; template switch
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Funding
- NACRP/NCI
- NIH [1R01 GM076186]
- NSF-IGERT [DGE-0114420]
- National Institute of General Medical Sciences [F31GM087120]
- [GM008659-11A1]
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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.
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