Noncanonical secondary structures arising from non-B DNA motifs are determinants of mutagenesis.

ABSTRACT: Somatic mutations show variation in density across cancer genomes. Previous studies have shown that chromatin organization and replication time domains are correlated with, and thus predictive of, this variation. Here, we analyze 1809 whole-genome sequences from 10 cancer types to show that a subset of repetitive DNA sequences, called non-B motifs that predict noncanonical secondary structure formation can independently account for variation in mutation density. Combined with epigenetic factors and replication timing, the variance explained can be improved to 43%-76%. Approximately twofold mutation enrichment is observed directly within non-B motifs, is focused on exposed structural components, and is dependent on physical properties that are optimal for secondary structure formation. Ther

SUBMITTER: Georgakopoulos-Soares I 

PROVIDER: S-EPMC6120622 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature