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Mutational signatures are jointly shaped by DNA damage and repair

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Title
Mutational signatures are jointly shaped by DNA damage and repair
Author(s)
Volkova N.V.; Meier B.; Gonzalez-Huici V.; Bertolini S.; Gonzalez S.; Vohringer H.; Abascal F.; Martincorena I.; Campbell P.J.; Anton Gartner; Gerstung M.
Subject
NUCLEOTIDE EXCISION-REPAIR, ; TRANSLESION SYNTHESIS, ; GENOMIC CHARACTERIZATION, ; POLYMERASE-ZETA, ; WHOLE-GENOME, ; PAIRED-END, ; C. ELEGANS, ; POL-ZETA, ; CANCER, ; REVEALS
Publication Date
2020-05
Journal
NATURE COMMUNICATIONS, v.11, no.1, pp.2169
Publisher
NATURE PUBLISHING GROUP
Abstract
© 2020, The Author(s). Cells possess an armamentarium of DNA repair pathways to counter DNA damage and prevent mutation. Here we use C. elegans whole genome sequencing to systematically quantify the contributions of these factors to mutational signatures. We analyse 2,717 genomes from wild-type and 53 DNA repair defective backgrounds, exposed to 11 genotoxins, including UV-B and ionizing radiation, alkylating compounds, aristolochic acid, aflatoxin B1, and cisplatin. Combined genotoxic exposure and DNA repair deficiency alters mutation rates or signatures in 41% of experiments, revealing how different DNA alterations induced by the same genotoxin are mended by separate repair pathways. Error-prone translesion synthesis causes the majority of genotoxin-induced base substitutions, but averts larger deletions. Nucleotide excision repair prevents up to 99% of point mutations, almost uniformly across the mutation spectrum. Our data show that mutational signatures are joint products of DNA damage and repair and suggest that multiple factors underlie signatures observed in cancer genomes
URI
https://pr.ibs.re.kr/handle/8788114/8627
DOI
10.1038/s41467-020-15912-7
ISSN
2041-1723
Appears in Collections:
Center for Genomic Integrity(유전체 항상성 연구단) > 1. Journal Papers (저널논문)
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