What is the Difference Between Topoisomerase I and II

The main difference between Topoisomerase I and II is that topoisomerase I cut one strand of the DNA double helix whereas topoisomerase II cut both strands of the DNA double helix. Furthermore, topoisomerase I do not require ATP hydrolysis while topoisomerase II requires ATP hydrolysis. Moreover, the three main subclasses of topoisomerase I are Type IA topoisomerase, Type IB topoisomerase, and Type IC topoisomerase while the two subclasses of topoisomerase II are Type IIA topoisomerase and Type IIB topoisomerase.

Topoisomerase I and II are two classes of enzymes responsible for fixing the topological problems associated with the DNA double helix. Generally, the three main types of such topological problems are supercoiling, knotting, and catenation. They are generated during DNA replication and transcription.

Key Areas Covered

1. What is Topoisomerase I
     – Definition, Subclasses, Function
2. What is Topoisomerase II
     – Definition, Subclasses, Function
3. What are the Similarities Between Topoisomerase I and II
     – Outline of Common Features
4. What is the Difference Between Topoisomerase I and II
     – Comparison of Key Differences

Key Terms

ATP, DNA Strand Breaks, Topoisomerase I, Topoisomerase II, Topological Problems

What is Topoisomerase I

Topoisomerase I is a class of topoisomerases exclusively found in eukaryotes. It is responsible for relaxing the stress of the DNA double helix generated due to either over winding or under winding. The main feature of this enzyme is that it generates single-strand breaks during the process. Once being cut, the cut DNA strand can rotate around the uncut DNA strand, reducing the stress. Another characteristic feature of topoisomerase I is that this enzyme does not require ATP hydrolysis for its function. After relaxation, the cut strand relegates.

Figure 1: The function of Topoisomerase in DNA Replication

The three subclasses of topoisomerase I are Type IA topoisomerase, Type IB topoisomerase, and Type IC topoisomerase.

• Type IA topoisomerase – responsible for removing negative supercoils. Its function depends on magnesium. Also, it forms a covalent intermediate with the 5’ end of the DNA strand which is going to be cut.
• Type IB topoisomerase – responsible for controlling the rotatory mechanism. It removes both positive and negative supercoils and forms an intermediate with the 3’ end.
• Type IC topoisomerase – responsible for removing both positive and negative supercoils and is involved in DNA repair. Same as Type IB topoisomerase, type IC topoisomerase forms an intermediate with the 3’ end.    

What is Topoisomerase II

Topoisomerase II is the other class of topoisomerase present in both eukaryotes and prokaryotes. Though its function is to relieve the stress in the DNA double helix, it produces double-strand breaks. Also, it uses ATP hydrolysis. However, the two main subclasses of topoisomerase II are Type IIA topoisomerase and Type IIB topoisomerase.

Figure 2: Human Topoisomerase IIA

• Type IIA topoisomerase – Four main types: E. coli DNA gyrase, which generates negative supercoils, E. coli topoisomerase IV, which relaxes negative supercoils, involving in decatenation, human topoisomerase IIα, which relaxes DNA during transcription, and human topoisomerase IIβ, which suppresses recombination.
• Type IIB topoisomerase – is responsible for relaxing both positive and negative supercoils.

Significantly, both subclasses of topoisomerases depend on magnesium ions, and they form the intermediate with the 5’ end. Especially, the function of topoisomerase II is essential for the functioning of all living organisms and cells that lack this enzyme are rendered unviable.

Similarities Between Topoisomerase I and II

• Topoisomerase I and II are two enzymes responsible for fixing topological problems of the DNA double helix.
• They act upon both over winded and under winded DNA.
• Moreover, their function is essential for the progression of DNA replication and transcription.
• Also, topoisomerases are classified based on the number of DNA strands cut by the enzyme during one round of action.

Difference Between Topoisomerase I and II

Definition

Topoisomerase I refers to the enzymes which cut one of the two strands of double-stranded DNA, relax the strand, and reanneal the strand while topoisomerase II refers to the enzymes which cut both strands of the DNA helix simultaneously in order to manage DNA tangles and supercoils. Thus, this is the main difference between topoisomerase I and II.

Type of DNA Strand Breaks

Another major difference between topoisomerase I and II is that topoisomerase I generates single-strand breaks while topoisomerase II generates double-strand breaks.

Occurrence

Furthermore, topoisomerase I occurs in eukaryotes while topoisomerase II occurs in both eukaryotes and prokaryotes.

Use of ATP

Topoisomerase I does not require ATP hydrolysis while topoisomerase II requires ATP hydrolysis. Hence, this is another difference between topoisomerase I and II.

Subclasses

The three main subclasses of topoisomerase I are Type IA topoisomerase, Type IB topoisomerase, and Type IC topoisomerase while the two subclasses of topoisomerase II are Type IIA topoisomerase and Type IIB topoisomerase.

Conclusion

Topoisomerase I is a class of topoisomerases exclusively present in eukaryotes. It produces single-strand breaks and does not require ATP for the relieving process. In contrast, topoisomerase II is a class of topoisomerases present in both eukaryotes and prokaryotes. It produces double-strand breaks using the energy from ATP. Both types of topoisomerases are responsible for reliving the stress of the DNA double helix generated during DNA replication and transcription. However, the main difference between topoisomerase I and II is the type of strand breaks generated by each type of enzyme.

References:

1. Banerji, S, and M Los. “Important Differences between Topoisomerase-I and -II Targeting Agents.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, Aug. 2006, Available Here.

Image Courtesy:

1. “DNA replication en” By LadyofHats Mariana Ruiz – Own work. Image renamed from File:DNA replication.svg (Public Domain) via Commons Wikimedia  
2. “1zxn” By Deposition authors: Wei, H., Ruthenburg, A.J., Bechis, S.K., Verdine, G.L.;visualization author: User:Astrojan (CC BY 4.0) via Commons Wikimedia

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