Topoisomerase II poisons represent some of the most important and widely prescribed anticancer drugs currently in clinical use. These drugs encompass a diverse group of natural and synthetic compounds that are commonly used to treat a variety of human malignancies. At the present time, six topoisomerase II-targeted anticancer agents are approved for use in the United States, and additional drugs are prescribed elsewhere in the world. These agents all act as traditional topoisomerase II poisons and function primarily by inhibiting enzyme-mediated DNA ligation.
Briefly describe what TopoII does and how it works. Explain what "inhibiting enzyme-mediated DNA ligation" means.
My thoughts for the first question are Type II topoisomerases cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. They use the hydrolysis of ATP. It changes the linking number of circular DNA by ±2. After the ends are cut, the ends of the DNA are separated and a second DNA duplex is passed through the break. The cut DNA is re- ligated. This allows the enzyme to increase or decrease the linking number of a DNA loop by 2 units. It also promotes chromosome disentanglement. Inhibiting enzyme-mediated DNA ligation means that it prevents the enzymes are not allowed to ligate. This is prevented by not allowing the formation of a phosphodiester bond.
Cancer cells grow much more rapidly than most cells in the body. What would be the consequence of "inhibiting enzyme-mediated DNA ligation" and why might this be particularly deleterious in cancer cells?
I am really unsure on this one.
I have looked at the Wikipedia answers to this question and they are wrong.