Topoisomerase

Topoisomerases are enzymes that participate in the overwinding or underwinding of DNA. The winding problem of DNA arises due to the intertwined nature of its double-helical structure. During DNA replication and transcription, DNA becomes overwound ahead of a replication fork. If left unabated, this torsion would eventually stop the ability of DNA or RNA polymerases involved in these processes to continue down the DNA strand.

In order to prevent and correct these types of topological problems caused by the double helix, topoisomerases bind to double-stranded DNA and cut the phosphate backbone of either one or both the DNA strands. This intermediate break allows the DNA to be untangled or unwound, and, at the end of these processes, the DNA backbone is resealed again. Since the overall chemical composition and connectivity of the DNA do not change, the tangled and untangled DNAs are chemical isomers, differing only in their global topology, thus the name for these enzymes. Topoisomerases are isomerase enzymes that act on the topology of DNA.

Bacterial topoisomerase and human topoisomerase proceed via the same mechanism for replication and transcription.

James C. Wang was the first to discover a topoisomerase when he identified E. coli topoisomerase I. Topo EC-codes are as follows: type I, EC 5.99.1.2; type II: EC 5.99.1.3. His discovery was made in the 1970s.

The double-helical configuration that DNA strands naturally reside, makes them difficult to separate and yet they must be separated by helicase enzymes, if other enzymes are to transcribe the sequences that encode proteins, or if chromosomes are to be replicated. In so-called circular DNA, in which double-helical DNA is bent around and joined in a circle, the two strands are topologically linked, or knotted. Otherwise identical loops of DNA, having different numbers of twists, are topoisomers, and cannot be interconverted by any process that does not involve the breaking of DNA strands. Topoisomerases catalyze and guide the unknotting or unlinking of DNA by creating transient breaks in the DNA using a conserved tyrosine as the catalytic residue.

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