Recent research has unveiled a promising new target for enhancing cancer therapies, particularly for patients whose cancers exhibit resistance to existing treatments. A team of scientists from the Indian Association for the Cultivation of Science (IACS) has focused on a DNA repair enzyme known as Tyrosyl-DNA phosphodiesterase 1 (TDP1), revealing its significant role in cancer cell survival following chemotherapy that targets Topoisomerase 1 (Top1) enzymes, such as Camptothecin and Topotecan.
While investigating how cancer cells repair DNA during cell division and respond to DNA damage induced by enzyme Topoisomerase 1 (Top1), the scientists discovered the critical roles of the proteins CDK1 and TDP1 that regulate the DNA repair process and repairs drug-induced trapped Top1 respectively.
The TDP1, was known to be a dedicated enzyme that repairs drug-induced trapped Top1 during the S phase when the DNA replicates, but its role and regulation during the mitotic phase were previously unknown. CDK1, on the other hand, the key regulatory kinase in the mitotic phase, was found to regulate the DNA repair process by phosphorylating TDP1, which enhances its ability to resolve Top1-DNA adducts.The scientists stressed that the phosphorylation event was crucial for efficient DNA repair during cell division, allowing cancer cells to survive Top1-targeted chemotherapy.