Microhomology directs diverse DNA break repair pathways and chromosomal translocations

Diana D Villarreal; Kihoon Lee; Angela Deem; Eun Yong Shim; Anna Malkova; Sang Eun Lee

doi:10.1371/journal.pgen.1003026

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Microhomology directs diverse DNA break repair pathways and chromosomal translocations

Journal article

Open access

Peer reviewed

Microhomology directs diverse DNA break repair pathways and chromosomal translocations

Diana D Villarreal, Kihoon Lee, Angela Deem, Eun Yong Shim, Anna Malkova and Sang Eun Lee

PLoS genetics, Vol.8(11), pp.e1003026-e1003026

2012

DOI: 10.1371/journal.pgen.1003026

PMCID: PMC3493447

PMID: 23144625

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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.

Chromosome Aberrations

Chromosomes - metabolism

DNA Breaks, Double-Stranded

DNA End-Joining Repair

DNA Repair

DNA Replication - genetics

DNA-Binding Proteins

DNA-Directed DNA Polymerase - genetics

DNA-Directed DNA Polymerase - metabolism

Recombination, Genetic

Saccharomyces cerevisiae

Translocation, Genetic - genetics

Details

Title: Subtitle: Microhomology directs diverse DNA break repair pathways and chromosomal translocations
Creators: Diana D Villarreal - Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States of America
Kihoon Lee
Angela Deem
Eun Yong Shim
Anna Malkova
Sang Eun Lee
Resource Type: Journal article
Publication Details: PLoS genetics, Vol.8(11), pp.e1003026-e1003026
DOI: 10.1371/journal.pgen.1003026
PMID: 23144625
PMCID: PMC3493447
NLM abbreviation: PLoS Genet
ISSN: 1553-7390
eISSN: 1553-7404
Publisher: Public Library Science
Grant note: GM083010 / NIGMS NIH HHS R01 GM083010 / NIGMS NIH HHS GM084242 / NIGMS NIH HHS R01 GM084242 / NIGMS NIH HHS GM071011 / NIGMS NIH HHS GM083010-02S1 / NIGMS NIH HHS R01 GM071011 / NIGMS NIH HHS F30 CA168173 / NCI NIH HHS
Language: English
Date published: 2012
Academic Unit: Biology
Record Identifier: 9984217417502771

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