The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing
نویسندگان
چکیده
Topoisomerase II is an essential enzyme that is required for virtually every process that requires movement of DNA within the nucleus or the opening of the double helix. This enzyme helps to regulate DNA under- and overwinding and removes knots and tangles from the genetic material. In order to carry out its critical physiological functions, topoisomerase II generates transient double-stranded breaks in DNA. Consequently, while necessary for cell survival, the enzyme also has the capacity to fragment the genome. The DNA cleavage/ligation reaction of topoisomerase II is the target for some of the most successful anticancer drugs currently in clinical use. However, this same reaction also is believed to trigger chromosomal translocations that are associated with specific types of leukemia. This article will familiarize the reader with the DNA cleavage/ligation reaction of topoisomerase II and other aspects of its catalytic cycle. In addition, it will discuss the interaction of the enzyme with anticancer drugs and the mechanisms by which these agents increase levels of topoisomerase II-generated DNA strand breaks. Finally, it will describe dietary and environmental agents that enhance DNA cleavage mediated by the enzyme.
منابع مشابه
Hairpin structures formed by alpha satellite DNA of human centromeres are cleaved by human topoisomerase IIα
Although centromere function has been conserved through evolution, apparently no interspecies consensus DNA sequence exists. Instead, centromere DNA may be interconnected through the formation of certain DNA structures creating topological binding sites for centromeric proteins. DNA topoisomerase II is a protein, which is located at centromeres, and enzymatic topoisomerase II activity correlate...
متن کاملTopoisomerase Inhibitors and Types of Them
Objective: In this paper, we have introduced topoisomerase inhibitors, mechanism of action and types of them. DNA topoisomerases are ubiquitous enzymes that catalyze essential enzymes to solve the topological problems accompanying key nuclear processes such as DNA replication, transcription, repair and chromatin assembly by introducing temporary single or double strand breaks in the DNA. Result...
متن کاملTopoisomerase Inhibitors and Types of Them
Objective: In this paper, we have introduced topoisomerase inhibitors, mechanism of action and types of them. DNA topoisomerases are ubiquitous enzymes that catalyze essential enzymes to solve the topological problems accompanying key nuclear processes such as DNA replication, transcription, repair and chromatin assembly by introducing temporary single or double strand breaks in the DNA. Result...
متن کاملInduction of mammalian DNA topoisomerase II dependent DNA cleavage by antitumor antibiotic streptonigrin.
Streptonigrin, a nonintercalative antitumor antibiotic, induced mammalian topoisomerase II dependent DNA cleavage in vitro. The cleavage activity of streptonigrin was comparable to that of demethylepipodophyllotoxin ethylidene-beta-D-glucoside at a low concentration (less than or equal to 10 microM) but one-third lower at a higher concentration (greater than 250 microM). Exposure of a reaction ...
متن کامل