Cytosine Methylation Affects the Mutability of Neighboring Nucleotides in Germline and Soma.

ABSTRACT: Methylated cytosines deaminate at higher rates than unmethylated cytosines, and the lesions they produce are repaired less efficiently. As a result, methylated cytosines are mutational hotspots. Here, combining rare polymorphism and base-resolution methylation data in humans, Arabidopsis thaliana, and rice (Oryza sativa), we present evidence that methylation state affects mutation dynamics not only at the focal cytosine but also at neighboring nucleotides. In humans, contrary to prior suggestions, we find that nucleotides in the close vicinity (±3 bp) of methylated cytosines mutate less frequently. Reduced mutability around methylated CpGs is also observed in cancer genomes, considering single nucleotide variants alongside tissue-of-origin-matched methylation data. In contras

SUBMITTER: Kusmartsev V 

PROVIDER: S-EPMC7153944 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature