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
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↵1 These authors contributed equally to this work.
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.
Keywords
- Inverted repeats
- acentric and dicentric chromosomes
- breakage–fusion–bridge cycle
- genome instability
- large palindromes
- template switch
Footnotes
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↵2 Corresponding author.
E-MAIL tweinert{at}email.arizona.edu; FAX (520) 621-3709.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1862709.
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Supplemental material is available at http://www.genesdev.org.
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- Received September 9, 2009.
- Accepted October 27, 2009.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press