bioRxivJClub
Carcinogen-induced DNA adducts amplify APOBEC mutagenesis through nucleotide excision repair
bioRxiv · · Preprint · Open access
Durfee, Stefanovska + 36 more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
NQO, a model tobacco carcinogen, triggers a 100-fold increase in APOBEC3B-catalyzed signature mutations and elevates oral carcinoma levels in vivo.
- Why it matters: Mutational processes are often treated as independent and additive, but tobacco carcinogens may interact with APOBEC-driven mutagenesis to shape cancer risk.
- What they did: The study combined in vivo NQO exposure with biochemical assays showing APOBEC3B catalyzes didyma, plus genetic tests requiring APOBEC3B and functional nucleotide excision repair (XPA in human cells, Rad14 in yeast).
- The result: Tumors from smokers show elevated APOBEC mutagenesis and didyma versus non-smokers, supporting a model where DNA-adducting carcinogens amplify APOBEC mutagenesis via nucleotide excision repair.
The findingWhy it mattersWhat they didThe result
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- Open access
- 4 cites