APOBEC3A induces DNA gaps through PRIMPOL and confers gap-associated therapeutic vulnerability
Ajinkya S. Kawale,
Xiaojuan Ran,
Parasvi S. Patel
et al.
Abstract:Mutation signatures associated with apolipoprotein B mRNA editing catalytic polypeptide-like 3A/B (APOBEC3A/B) cytidine deaminases are prevalent across cancers, implying their roles as mutagenic drivers during tumorigenesis and tumor evolution. APOBEC3A (A3A) expression induces DNA replication stress and increases the cellular dependency on the ataxia telangiectasia and Rad3-related (ATR) kinase for survival. Nonetheless, how A3A induces DNA replication stress remains unclear. We show that A3A induces replicat… Show more
“…Of note, IDH1/2 mutants were recently shown to induce ssDNA gaps ( 125 ). Expression of APOBEC3A, a driver of mutagenesis in multiple tumor types, also induces ssDNA gaps and confers PARPi sensitivity ( 129 ).…”
Section: Expanding Application Of Parpis Beyond Brca1/2-mutated Cancersmentioning
“…Of note, IDH1/2 mutants were recently shown to induce ssDNA gaps ( 125 ). Expression of APOBEC3A, a driver of mutagenesis in multiple tumor types, also induces ssDNA gaps and confers PARPi sensitivity ( 129 ).…”
Section: Expanding Application Of Parpis Beyond Brca1/2-mutated Cancersmentioning
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