The data presented here, combined with critical review of recent studies of UHRF1 domain function, demonstrate that methyllysine recognition of LIG1 (and histone H3) by UHRF1 is not required for the maintenance of cancer cell DNA methylation patterning through cell divisions and that disruption of this function, alone, may not be a viable strategy toward antagonizing aberrant DNA methylation patterns maintained by UHRF1 in cancer cells. The gene discussed is LIG1; the disease is cancer.