Classes
Topoisomerases can fix these topological problems and are separated into two types separated by the number of strands cut in one round of action: Both these classes of enzyme utilize a conserved tyrosine. However these enzymes are structurally and mechanistically different. For a video of this process see: http://www.youtube.com/watch?v=EYGrElVyHnU&feature=related.
- Type I topoisomerase cuts one strand of a DNA double helix, relaxation occurs, and then the cut strand is reannealed. Cutting one strand allows the part of the molecule on one side of the cut to rotate around the uncut strand, thereby reducing stress from too much or too little twist in the helix. Such stress is introduced when the DNA strand is "supercoiled" or uncoiled to or from higher orders of coiling. Type I topoisomerases are subdivided into two subclasses: type IA topoisomerases, which share many structural and mechanistic features with the type II topoisomerases, and type IB topoisomerases, which utilize a controlled rotary mechanism. Examples of type IA topoisomerases include topo I and topo III. In the past, type IB topoisomerases were referred to as eukaryotic topo I, but IB topoisomerases are present in all three domains of life. It is interesting to note that type IA topoisomerases form a covalent intermediate with the 5' end of DNA, while the IB topoisomerases form a covalent intermediate with the 3' end of DNA. Recently, a type IC topoisomerase has been identified, called topo V. While it is structurally unique from type IA and IB topoisomerases, it shares a similar mechanism with type IB topoisomerase.
- Type II topoisomerase cuts both strands of one DNA double helix, passes another unbroken DNA helix through it, and then reanneals the cut strands. It is also split into two subclasses: type IIA and type IIB topoisomerases, which share similar structure and mechanisms. Examples of type IIA topoisomerases include eukaryotic topo II, E. coli gyrase, and E. coli topo IV. Examples of type IIB topoisomerase include topo VI. Type II topisomerases utilize ATP hydrolysis.
| Topoisomerase | IA | IB | IIA | IIB |
|---|---|---|---|---|
| Metal Dependence | Yes | No | Yes | Yes |
| ATP Dependence | No | No | Yes | Yes |
| Single- or Double-Stranded cleavage? | SS | SS | DS | DS |
| Cleavage Polarity | 5' | 3' | 5' | 5' |
| Change in L | ±1 | ±N | ±2 | ±2 |
Both type I and type II topoisomerases change the linking number (L) of DNA. Type IA topoisomerases change the linking number by one, type IB and type IC topoisomerases change the linking number by any integer, while type IIA and type IIB topoisomerases change the linking number by two.
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