title: 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.
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.
authors.affiliation: Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Paek
authors.forename: Salma
authors.initials: S
authors.lastname: Kaochar
authors.forename: Hope
authors.initials: H
authors.lastname: Jones
authors.forename: Aly
authors.initials: A
authors.lastname: Elezaby
authors.forename: Lisa
authors.initials: L
authors.lastname: Shanks
authors.forename: Ted
authors.initials: T
authors.lastname: Weinert
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics*; D053960:DNA Breaks; D004261:DNA Replication / Q000235:genetics*; D004271:DNA, Fungal / Q000235:genetics*; D042822:Genomic Instability; D055029:Inverted Repeat Sequences / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins