Local sequence context at <i>KRAS</i> codons modulates DNA repair efficiency: insights from molecular dynamics simulations.

ABSTRACT:

Introduction

Benzo[a]pyrene diol-epoxide (BPDE)-induced DNA adducts contribute to the disproportionate mutagenesis of codon 12 in the KRAS gene, driven by preferential DNA damage and impaired repair. Codon susceptibility, however, extends beyond oncogenic hotspots, suggesting that BPDE lesions may serve as biomarkers of individual DNA repair capacity and cancer risk. While the genotoxic effects of tobacco smoke are well characterised, their influence on DNA repair remains underexplored.

Methods

Here, we modelled BPDE-adducted KRAS sequences at codons 12 and 14, which have been suggested to exhibit differential repair rates, to assess local helical distortion and its impact on nucleotide excision repair (NER).

Results

We show that BPDE adduction at codon

SUBMITTER: Davies J 

PROVIDER: S-EPMC12441607 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature