title: Microhomology directs diverse DNA break repair pathways and chromosomal translocations.
abstract: Chromosomal structural change triggers carcinogenesis and the formation of other genetic diseases. The breakpoint junctions of these rearrangements often contain small overlapping sequences called "microhomology," yet the genetic pathway(s) responsible have yet to be defined. We report a simple genetic system to detect microhomology-mediated repair (MHMR) events after a DNA double-strand break (DSB) in budding yeast cells. MHMR using >15 bp operates as a single-strand annealing variant, requiring the non-essential DNA polymerase subunit Pol32. MHMR is inhibited by sequence mismatches, but independent of extensive DNA synthesis like break-induced replication. However, MHMR using less than 14 bp is genetically distinct from that using longer microhomology and far less efficient for the repair of distant DSBs. MHMR catalyzes chromosomal translocation almost as efficiently as intra-chromosomal repair. The results suggest that the intrinsic annealing propensity between microhomology sequences efficiently leads to chromosomal rearrangements.
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Diana D
authors.initials: DD
authors.lastname: Villarreal
authors.forename: Kihoon
authors.initials: K
authors.lastname: Lee
authors.forename: Angela
authors.initials: A
authors.lastname: Deem
authors.forename: Eun Yong
authors.initials: EY
authors.lastname: Shim
authors.forename: Anna
authors.initials: A
authors.lastname: Malkova
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Lee
mesh_terms: D002869:Chromosome Aberrations; D002875:Chromosomes / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D059766:DNA End-Joining Repair; D004260:DNA Repair; D004261:DNA Replication / Q000235:genetics*; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase