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.
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.
Paek
Andrew L
AL
Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
Kaochar
Salma
S
Jones
Hope
H
Elezaby
Aly
A
Shanks
Lisa
L
Weinert
Ted
T
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
D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins