Interestingly, in addition to the nick joining activity, we have now verified that human DNA ligase I also possess DNA relaxation activity, just like topoisomerase I. We, therefore, hypothesize that hLigI may be involved in the development of resistance towards topoisomerase I inhibitors and propose that appropriate hLigI inhibitors when used in combination with Top1 inhibitors, may be useful for the successful treatment of topoisomerase resistant colorectal cancers. This evidence concerns the gene LIG1 and colorectal cancer.