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Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions

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Title
Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions
Author(s)
Sinha S.; Li F.; Villarreal D.; Shim J.H.; Yoon S.; Kyungjae Myung; Shim E.Y.; Lee S.E.
Publication Date
2017-04
Journal
PLOS GENETICS, v.13, no.4, pp.e1006714 -
Publisher
PUBLIC LIBRARY SCIENCE
Abstract
Microhomology (MH) flanking a DNA double-strand break (DSB) drives chromosomal rearrangements but its role in mutagenesis has not yet been analyzed. Here we determined the mutation frequency of a URA3 reporter gene placed at multiple locations distal to a DSB, which is flanked by different sizes (15-, 18-, or 203-bp) of direct repeat sequences for efficient repair in budding yeast. Induction of a DSB accumulates mutations in the reporter gene situated up to 14-kb distal to the 15-bp MH, but more modestly to those carrying 18- and 203-bp or no homology. Increased mutagenesis in MH-mediated end joining (MMEJ) appears coupled to its slower repair kinetics and the extensive resection occurring at flanking DNA. Chromosomal translocations via MMEJ also elevate mutagenesis of the flanking DNA sequences 7.1 kb distal to the breakpoint junction as compared to those without MH. The results suggest that MMEJ could destabilize genomes by triggering structural alterations and increasing mutation burden. © 2017 Sinha et al
URI
http://pr.ibs.re.kr/handle/8788114/4178
DOI
10.1371/journal.pgen.1006714
ISSN
1553-7390
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > Journal Papers (저널논문)
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