Topoisomerase- Definition, Types, Structure, Functions, Mechanism


DNA is a complex molecule that stores and transmits genetic information in all living cells. However, DNA also faces many topological challenges that can affect its structure and function. For instance, DNA can become overwound or underwound, tangled or knotted, or linked with other DNA molecules. These topological problems can interfere with vital processes such as DNA replication, transcription, recombination and chromosome segregation.

To solve these problems, cells rely on a group of enzymes called topoisomerases. Topoisomerases are able to change the topology of DNA by making transient breaks in one or both strands of the DNA backbone and allowing the DNA to pass through the gap. By doing so, they can relax or introduce supercoils, unlink or link DNA molecules, and unknot or knot DNA loops. Topoisomerases are essential for cell survival and gene activity .

Topoisomerases are classified into two major types based on their mechanism of action: type I and type II. Type I topoisomerases cut one strand of DNA and change the linking number by one unit. Type II topoisomerases cut both strands of DNA and change the linking number by two units. Type I topoisomerases do not require ATP (except for reverse gyrase), while type II topoisomerases are ATP-dependent. Both types of topoisomerases use a conserved tyrosine residue to form a covalent bond with the DNA phosphate during the cleavage and religation steps .

The first topoisomerase was discovered in bacteria by James Wang in 1971. It is now called Escherichia coli (E. coli) topoisomerase I and belongs to the type IA family of enzymes. Later, a similar enzyme was found in eukaryotic cells by James Champoux and Renato Dulbecco. It is called eukaryotic topoisomerase I and belongs to the type IB family of enzymes. The first type II topoisomerase to be discovered was DNA gyrase from bacteria by Martin Gellert and coworkers in 1976. DNA gyrase is unique among topoisomerases in that it introduces negative supercoils into DNA. Other type II topoisomerases were subsequently identified from bacterial viruses and eukaryotes .

In this article, we will explore the definition, structure, types, functions and mechanism of action of topoisomerases in more detail. We will also discuss the inhibition of topoisomerases by small molecules and their clinical significance.