In light of our observations above demonstrating gap ligation in the case of inefficient incorporation of dNTP or rNTP mismatches by polβ wild-type, in the present study, we examined the impact of correct nucleotide insertions by polβ cancer-associated variants Y265C, E288K and E295K on nick sealing by LIG1 in coupled assays. The gene discussed is LIG1; the disease is cancer.