Which of the following reactions with covalently closed, circular DNA (cccDNA) does NOT result in a new linking number? A. incub
ation with a type II topoisomerase B. incubation with a type I topoisomerase C. incubation with ethidium D. brief incubation with DNase I followed by resealing the breaks in the phosphodiester backbone with another enzyme (DNA ligase)
Human topoisomerase I plays an important role in removing positive DNA supercoils that accumulate ahead of replication forks. It also is the target for camptothecin-based anticancer drugs that act by increasing levels of topoisomerase I-mediated DNA scission. Evidence suggests that cleavage events most likely to generate permanent genomic damage are those that occur ahead of DNA tracking systems. Therefore, it is important to characterize the ability of topoisomerase I to cleave positively supercoiled DNA. Results confirm that the human enzyme maintains higher levels of cleavage with positively as opposed to negatively supercoiled substrates in the absence or presence of anticancer drugs. Enhanced drug efficacy on positively supercoiled DNA is due primarily to an increase in baseline levels of cleavage. Sites of topoisomerase I-mediated DNA cleavage do not appear to be affected by supercoil geometry. However, rates of ligation are slower with positively supercoiled substrates. Finally, intercalators enhance topoisomerase I-mediated cleavage of negatively supercoiled substrates but not positively supercoiled or linear DNA. We suggest that these compounds act by altering the perceived topological state of the double helix, making underwound DNA appear to be overwound to the enzyme, and propose that these compounds be referred to as ‘topological poisons of topoisomerase I’
The best treatment for an acute thigh contusion is to wrap your thigh with a wet bandage to insulate skin. This is important because, you could become more injured if you didn't do proper steps to the healing process.
In addition to fighting fires, firefighters also treat sick or injured people, report to car accidents, extricate people from damaged motor vehicles, and assist at hazardous materials spills.
