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Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions
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نویسنده
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sinha s. ,li f. ,villarreal d. ,shim j.h. ,yoon s. ,myung k. ,shim e.y. ,lee s.e.
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منبع
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plos genetics - 2017 - دوره : 13 - شماره : 4
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چکیده
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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.
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آدرس
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department of molecular medicine,institute of biotechnology,university of texas health science center at san antonio,san antonio,tx, United States, department of molecular medicine,institute of biotechnology,university of texas health science center at san antonio,san antonio,tx, United States, children’s hospital of san antonio,baylor college of medicine,san antonio,tx, United States, korea institute of radiological & medical sciences (kirams),75 nowon-ro,nowon-gu,seoul, South Korea, department of biological science,school of life sciences,ulsan national institute of science and technology (unist),ulsan,44818, South Korea, department of biological science,school of life sciences,ulsan national institute of science and technology (unist),ulsan,44818,south korea,center for genomic integrity,institute for basic science,ulsan,44818, South Korea, department of radiation oncology,university of texas health science center at san antonio,san antonio,tx, United States, department of molecular medicine,institute of biotechnology,university of texas health science center at san antonio,san antonio,tx,united states,department of radiation oncology,university of texas health science center at san antonio,san antonio,tx, United States
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Authors
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