Author:
Mohamed Nabil Helaly Ahmed,Ghorab Doaa
Abstract
Topoisomerase 1 is the main enzyme playing an important role in relaxing. The supercoiled DNA strands allow the replication fork to transcribe the DNA to RNA and finally control protein production in active and replicating cells. Blocking this essential machinery is a cornerstone mechanism in treating tumors, such as liver, breast, and metastatic colorectal carcinoma. Irinotecan is a topoisomerase inhibitor that blocks the replication ending in DNA break and tumor cell death. This chemotherapy has been successfully used in combination to overcome metastatic colorectal carcinoma. The topoisomerase-1 inhibitor makes a protein DNA complex stuck with the replicating fork creating a single DNA break, unlike topoisomerase-2, which is responsible for double DNA break. This inhibitor is exposed to drug resistance with complex machinery. Drug resistance can occur as a result of altered DNA methylation, changes in topoisomerase expression, histone recombination, or drug export pump. High expression of topoisomerase-1 is a marker of the number of tumors suggesting multiple roles of topoisomerase-1.
Reference101 articles.
1. Bush NG, Evans-Roberts K, Maxwell A. DNA topoisomerases. EcoSal Plus. 2015;6:2
2. Nitiss JL, Kiianitsa K, Sun Y, Nitiss KC, Maizels N. Topoisomerase assays. Current Protocol. 2021;1(10):e250
3. Husain I, Mohler JL, Seigler HF, Besterman JM. Elevation of topoisomerase I messenger RNA, protein, and catalytic activity in human tumors: Demonstration of tumor-type specificity and implications for cancer chemotherapy. Cancer Research. 1994;54(2):539-546
4. Zhao C, Yasui K, Lee CJ, Kurioka H, Hosokawa Y, Oka T, et al. Elevated expression levels of NCOA3, TOP1, and TFAP2C in breast tumors as predictors of poor prognosis. Cancer. 2003;98(1):18-23
5. Humbert N, Martien S, Augert A, Da Costa M, Mauen S, Abbadie C, et al. A genetic screen identifies topoisomerase 1 as a regulator of senescence. Cancer Research. 2009;69(10):4101-4106