postoperative weekly adjuvant bolus of 5-fluorouracil/leucovorin (FU/LV) or else with irinotecan+FU/LV and were followed up for 8 years. Eleven percent of the tumors were deficient for DNA repair enzyme MRE11 due to a deletion of a string of thymidines in the DNA sequence of the MRE11 gene. The addition of irinotecan to FU/LV in the treatment protocol resulted in MRE11-deficient patients having better long-term disease free survival than patients with wild-type MRE11 (though the effect was small), indicating some degree of synthetic lethality between irinotecan-induced TOP1 inactivation and MRE11 deficiency. There are a number of pre-clinical studies indicating synthetic lethality of irinotecan with other genetic or epigenetic DNA repair deficiencies common in cancers. For instance, the DNA repair gene ATM is frequently hypermethylated (silenced) in many cancers (see hypermethylation of ATM in cancers). A 2016 study showed that low expression of the ATM protein in gastric cancer cells in vitro and in a mouse model caused increased sensitivity to inactivation by irinotecan compared to cells with high expression of ATM. This indicates synthetic lethality of ATM deficiency with irinotecan-mediated TOP1 deficiency. Another pre-clinical effort was a screening study to find a compound that would be synthetically lethal with a deficiency of N-myc downstream regulated gene 1 (NDRG1) expression. NDRG1 is a metastasis-suppressor gene in prostate cancer, and appears to have a role in DNA repair. Screening of 3360 compounds revealed that irinotecan-mediated TOP1 deficiency (and one other compound, cetrimonium bromide) exhibit synthetic lethality with NDRG1 deficiency in prostate cancer cells. DNA repair Exposure of human HeLA cells to UVB irradiation specifically stimulates the formation of covalent complexes between topoisomerase I and DNA. Topoisomerase I appears to have a direct role in nucleotide excision repair, a process that removes UVB-induced, and other, DNA damages. Interactions TOP1 has been shown to interact with: ASF/SF2, BTBD1, BTBD2, Nucleolin, P53, and UBE2I. See also Type I topoisomerase Topoisomerase References External links