C. elegans whole-genome sequencing reveals mutational signatures related to carcinogens and DNA repair deficiency.

ABSTRACT: Mutation is associated with developmental and hereditary disorders, aging, and cancer. While we understand some mutational processes operative in human disease, most remain mysterious. We used Caenorhabditis elegans whole-genome sequencing to model mutational signatures, analyzing 183 worm populations across 17 DNA repair-deficient backgrounds propagated for 20 generations or exposed to carcinogens. The baseline mutation rate in C. elegans was approximately one per genome per generation, not overtly altered across several DNA repair deficiencies over 20 generations. Telomere erosion led to complex chromosomal rearrangements initiated by breakage-fusion-bridge cycles and completed by simultaneously acquired, localized clusters of breakpoints. Aflatoxin B1 induced substitutions of guanines i

SUBMITTER: Meier B 

PROVIDER: S-EPMC4199376 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature