DNA topoisomerases are responsible for DNA unlinking and these ubiquitous enzymes play critical roles in many biological processes involving DNA. There are two types of DNA topoisomerases, type I and type II. Type I topoisomerases break one DNA strand of duplex DNA to allow either the passage of the other DNA strand through the break or the rotation of downstream DNA duplex about the break, and then reseal the broken strand. There are three subtypes of type I topoisomerases: type IA, type IB, and type IC. Type IA topoisomerases require a nick or a single-stranded region to bind to DNA. They cleave one strand of duplex DNA, covalently attach the active-site tyrosine to a 5′-phosphoryl group, and utilize the ‘strand passage’ mechanism to alter DNA topology. 
In contrast, types IB and IC topoisomerases cleave one strand of duplex DNA, covalently attach its active-site tyrosine to a 3′-phosphoryl group, and utilize the ‘swivel’ mechanism to relax DNA supercoils. Type II topoisomerases alter the linking number in steps of two by breaking both DNA strands of duplex DNA [referred to as the ‘Gate (G)-segment’], passing another duplex DNA [referred to as the ‘Transfer (T)-segment’] through the break or the ‘DNA gate’, and then resealing the broken DNA strands. There are two subtypes of type II topoisomerases, type IIA and type IIB. Topoisomerase VI belongs to the type IIB subtype, while all other type II topoisomerases belong to the type IIA subtype. Each subtype of topoisomerase is structurally and functionally conserved and forms a protein family.


1.Delgado JL, et al. Biochem J. 2018;475(2):373–398.