Sequence context-specific mutagenesis and base excision repair

Base excision repair (BER) is critical for the maintenance of genome stability because it repairs at least 20,000 endogenously generated DNA lesions/cell/d. Several enzymes within the BER pathway exhibit sequence context dependency during the excision and DNA synthesis steps of repair. New evidence is emerging that germ line and tumor-associated variants of enzymes in this repair pathway exhibit sequence context dependence that is different from their ancestral counterparts. We review what is known about the ancestral and variant BER proteins within various sequence contexts. We suggest that altering the sequence context preferences of BER proteins could give rise to rare cellular variants that might have a selective advantage in response to environmental exposure or to the tumor microenvironment.