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[[Image:Topoisomerase I.png|thumb|Topoisomerase I solves the problem caused by tension generated by winding/unwinding of DNA. It wraps around DNA and makes a cut permitting the helix to spin. Once DNA is relaxed, topoisomerase reconnects broken strands ({{PDB|1a36}})]]
'''Topoisomerases''' (type I: {{EC number|5.99.1.2}}, type II: {{EC number|5.99.1.3}}) are  [[isomerase]] [[enzymes]] that acts on the [[DNA topology|topology]] of [[DNA]]. It was first discovered by Harvard Professor [[James C. Wang]].<ref>http://www.nasonline.org/site/PageServer?pagename=AWARDS_molbio]</ref>

==Function==
The [[Double helix|double-helical]] 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)|transcribe]] the [[DNA sequence|sequences]] that [[genetic code|encode]] [[protein]]s, or if [[chromosomes]] are to be [[DNA replication|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 [[Knot theory|knotted]]. Otherwise identical loops of DNA having different numbers of twists are [[topoisomer]]s, 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|fluoroquinolone]] [[antibiotic]]s act by disrupting the function of bacterial type II topoisomerases.  

Some [[chemotherapy]] drugs work by interfering with topoisomerases in [[cancer]] [[Cell (biology)|cells]]: 
* 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|supercoiling]], [[knotting]] and [[catenation]]. When outside of [[DNA replication|replication]] or [[Transcription (genetics)|transcription]] 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==
<references/>
* Champoux JJ (2001) DNA Topoisomerases: Structure, Function, and Mechanism ''Annual Review of Biochemistry'' '''70''': 369-413[http://www.fhcrc.org/science/labs/stoddard/MCB_542/champoux_review_2001.pdf]

==See also==

* [[DNA topology]]
* [[Supercoil]]
* [[TOP1]]

==External links==

* {{MeshName|DNA+Topoisomerases}}

{{Enzymes}}
{{Topoisomerases}}
{{DNA replication}}
{{Autoantigens}}

[[Category:EC 5.99.1]]

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