DNA Topoisomerases (TOP) are enzymes capable of solving topological problems in DNA molecules during replication, transcription, recombination and chromatin remodeling by introducing temporary breaks in the DNA. Besides that, these enzymes can modulate the level of DNA supercoiling to facilitate protein interaction with the molecule and to prevent supercoiling relationed stress. There are several types of topoisomerases that are different in structure and function, but basically, the topos are divided based on whether they catalyze single- (type I) or double-stranded (type II) DNA breaks.
Within type two topoisomerases there are two classes: A and B. Class B is found only in archaea and type A is present in eukarya and bacteria. Humans have two types of 2A topoisomerases: isoforms alpha and beta. Topoisomerase 2 alpha has a larger role in chromosome segregation and DNA replication and tends to be expressed in more proliferating tissues, which makes topoisomerase 2 alpha a cancer cell marker and the target of anti-cancer drugs. Top 2A alpha is responsible for the selective cleaving, rearranging and religation of DNA strands, which helps untangle the chromosome, thereby changing the state of DNA in the cell.
Mammalian DNA topoisomerase IIα (human) IIA is a homodimeric protein, in whitch each subunit structure can be broken down into three major components that are connected by hinged like regions: the N gate, the DNA gate and the C gate.
Function
General Aspects
Disease
Relevance
Structural highlights
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