Topoisomerase

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Topoisomerases (type I: , type II: ) are isomerase enzymes that acts on the DNA topology of DNA. It was first discovered by Harvard Professor James C. Wang.http://www.nasonline.org/site/PageServer?pagename=AWARDS_molbio]

Function The Double helix configuration that DNA strands naturally reside in makes them difficult to separate, and yet they must be separated by helicase proteins if other enzymes are to Transcription (genetics) the DNA sequence that genetic code proteins, or if chromosomes are to be DNA replication. 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 Knot theory. 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 of DNA.

The insertion of viral DNA into chromosomes and other forms of recombination can also require the action of topoisomerases.

Clinical significance See also topoisomerase inhibitor Many drugs operate through interference with the topoisomerases. The broad-spectrum Quinolone antibiotics act by disrupting the function of bacterial type II topoisomerases.

Some chemotherapy drugs work by interfering with topoisomerases in cancer Cell (biology):

type 1 is inhibited by irinotecan and topotecan.
type 2 is inhibited by etoposide and teniposide.

Topoisomerase I is the antigen recognized by Anti Scl-70 antibodies in scleroderma.

Topological problems There are three main types of topology; DNA supercoil, knotting and catenation. When outside of DNA replication or Transcription (genetics) DNA needs to be kept as compact as possible and these three states help this cause. However when transcription or replication occur DNA needs to be free and these states seriously hinder the processes.

Types Topoisomerases can fix these topological problems and are separated into two types separated by the number of strands cut in one round of action:

Type I topoisomerase cuts one strand, passes the other through it then reanneals the cut strand.
Type II topoisomerase cuts both strands, and passes an unbroken double strand through it then reanneals the cut strand.

Both type I and type II topoisomerases change the linking number of DNA.

References

Champoux JJ (2001) DNA Topoisomerases: Structure, Function, and Mechanism Annual Review of Biochemistry 70: 369-413