POLB and cancer: Further structure/function studies with both BER DNA ligases (I and IIIα) are required for all other possible noncanonical base pairs at the 3′-end of the nick DNA to comprehensively understand how human DNA ligases discriminate against the mutagenic repair intermediates containing mismatched or damaged 3′-end which could be formed due to the aberrant gap filling by polβ, which has been reported to be increased in the cancer-associated variants with reduced fidelity15,16.