Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures

PURPOSE: Base excision repair (BER) is the predominant pathway for repairing non‑bulky oxidized and alkylated DNA base lesions, and its fidelity depends on the coordinated action of lesion‑specific DNA glycosylases and downstream repair enzymes. This review aims to summarize recent structural, biochemical, and genomic insights into three base excision repair enzymes, MUTYH DNA glycosylase, NTHL1 DNA glycosylase, and DNA polymerase β. CONCLUSION: This review outlines how MUTYH, NTHL1 and DNA polymerase β protect the genome from mutagenesis, highlights major germline variants associated with disease, and synthesizes the current knowledge on the characteristic single base substitution (SBS) mutational signatures that occur when these repair enzymes are dysfunctional.