Essay On Topoisomerase

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DNA supercoiling occurs in all cells that undergo genetic processing. This event blocks replicative and transcriptional machinery from binding to the DNA helix, which proves detrimental to the cell. However, current research is beginning to show that not all affects of supercoiling produce negative results. These studies prove that different coiling patterns increase the efficiency of epigenetic processes such as methylation and acetylation. Topoisomerase, a post-transcriptional monomeric enzyme, solves the winding problem of the double helix by implementing transient cuts in the genome. As these cuts build up, the genome is essentially fragmented by the enzyme and the cell is unable to express essential genes; this genomic degradation by topoisomerase serves as a viable pathway into cancer research. This review article synthesizes the many ideas surrounding topological cellular events, and presents a new direction for research on chromatin modification in cancerous cells. However, due to the time constraints of the project, this article will not thoroughly discuss the mechanistic process of the replication pathway.

INTRODUCTION:

A linear strand of DNA experiences tremendous torsional forces when undergoing replication. The replicative machinery applies a force as it unwinds the double strand and splits the DNA apart to expose the genetic information. The helicase enzyme is responsible for putting such tension on the double helix and causing the event known as supercoiling (1). This event is troublesome for the cell because it can cause certain regions of the genome to be inaccessible to the replicative enzymes. As a result, the vital genetic information contained in these locations goes unread, leading to mutation in the daugh...

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...ertions, deletions, and aberrations. Introducing the proper inhibitory factors would force topoisomerase to leave a mutated genome partially degraded, thus blocking the replication of cancerous cells (3). Catalytic topoisomerase inhibitors are a heterogeneous group of compounds that interfere with the binding of DNA and topoisomerase, stabilize noncovalent DNA-topoisomerase complexes, or inhibit ATP binding (9). Most catalytic inhibitors have additional targets and activities that likely contribute to their biological effects. Topoisomerase poisons can be used, along with inhibitors, to induce cellular tumor suppression. Poisons increase the steady-state concentration of their covalent DNA cleavage complexes; this action converts topoisomerase into a physiological toxin that introduces high levels of transient protein-associated breaks in the genome of treated cells.

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