Microhomology-mediated end joining induces hypermutagenesis at breakpoint junctions.
PLoS Genet
; 13(4): e1006714, 2017 04.
Article
en En
| MEDLINE
| ID: mdl-28419093
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ADN
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Mutagénesis
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Proteínas de Saccharomyces cerevisiae
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Reparación del ADN por Unión de Extremidades
Idioma:
En
Revista:
PLoS Genet
Asunto de la revista:
GENETICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos