Damage pinpointing reveals sequence-dependent DNA repair kinetics as a major determinant of mutagenesis
The widely used "tobacco-mimicking" genotoxin 4-Nitroquinoline 1-oxide (4NQO) induces DNA adducts which are removed by nucleotide excision repair yet its repair has not been analyzed genome-wide. Here we map repair of 4NQO-induced DNA adducts in human cells with a method precisely pinpointing the damaged-base position thus allowing for analysis of the nucleotide sequence context of the genome-wide repair events. We generated repair maps at different time points in wild type and nucleotide excision repair-deficient cells and found that there is a strong correlation between highly mutagenic sites and late-repaired sequence contexts.
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