Dna Topoisomerases

Identical loops of DNA having different numbers of twists are topoisomers, that is, molecules with the same formula but different topologies, and their interconversion requires the breaking of DNA strands. DNA topoisomerases are enzymes that regulate the three-dimensional geometry (topology) of DNA, leading to the interconversion of its topological isomers and to its relaxation. This is related to the regulation of DNA supercoiling, which is essential to DNA transcription and replication, when the DNA helix must unwind to permit the proper function of the enzymatic machinery involved in these processes.

Topoisomerase I breaks a single DNA strand while topoisomerase II breaks both strands and requires ATP for full activity. In both cases, the enzyme is covalently attached to the DNA through tyrosine residues in the active site. These are transient, easily reversible linkages, and for this reason this covalently bound structure is known as the 'cleavable complex'. Afterwards, another DNA strand passes through the transient break in the DNA, and finally the DNA break is resealed. The end result of the reaction is a DNA molecule which is chemically unchanged, but closed in a different topology. The normal catalytic cycle of both types of topoisomerases involves two transesterification steps, one for the cleavage and other for the religation process. In the cleavage reaction, nucleo-philic attack of an active site tyrosine forms a covalent bond with DNA by nucleophilic attack of its hydroxy group to a phosphate group of the phosphodie-ster DNA backbone. In the religation step, the 5'-hydroxyl group from deoxyri-bose attacks the previously formed tyrosine phosphate.

Topoisomerases are crucial for the several DNA functions (e.g. replication and transcription) that require the DNA to be unravelled, a process that generates tension and entanglement in DNA. Drugs that inhibit the topoisomerases include some of the most widely used anticancer drugs.39 On the other hand, topoisomer-ase poisons may trigger chromatid breakage to inactivate the ataxia telangiectasia (AT) gene function, disable cell cycle control, and induce genetic instability.40 In this connection, some alarming studies have been published, suggesting that maternal exposure to low doses of dietary topoisomerase II poisons, including bioflavonoids such as genistein or quercetin, may contribute to the development of infant leukaemia.41

How To Deal With Rosacea and Eczema

How To Deal With Rosacea and Eczema

Rosacea and Eczema are two skin conditions that are fairly commonly found throughout the world. Each of them is characterized by different features, and can be both discomfiting as well as result in undesirable appearance features. In a nutshell, theyre problems that many would want to deal with.

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