The deaminase APOBEC3B triggers the death of cells lacking uracil DNA glycosylase

This is the authors' abstract. We don't add key points for this paper.

Significance APOBEC3B (A3B) is overexpressed in multiple tumor types and a major source of mutation by converting DNA cytosines to uracils. A3B-positive tumors are often more heterogenous and result in poor clinical outcomes. We show that a proportion of A3B-catalyzed uracil lesions is repaired by uracil DNA glycosylase 2 (UNG)-driven base excision repair and that rendering cells UNG-defective leads to cytotoxicity. This cell death mechanism requires uracil processing by mismatch repair proteins and functional p53. Our results indicate that UNG inhibition could be a strategy to kill a subset of A3B-positive tumors.