Strand-resolved mutagenicity of DNA damage and repair.

ABSTRACT: DNA base damage is a major source of oncogenic mutations¹. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation². Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair. Despite distinct mechanisms of leading and lagging strand replication^3,4, we observe identical fidelity and damage tolerance for both strands. For small alkylation adducts of DNA, our results support a model in which the same translesion polymerase is recruited on-the-fly to both replication strands, starkly contrasting the strand asymmetric tolerance of bulky UV-induced adducts⁵. The accumulation of multiple distinct mu

SUBMITTER: Anderson CJ 

PROVIDER: S-EPMC11186772 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature