DNA topoisomerase

DNA topoisomerases are essential enzymes that regulate the overwinding or underwinding (“supercoiling”) of double-stranded DNA. They solve critical topological problems during fundamental cellular processes such as replication, transcription, recombination, chromosome condensation/segregation, and chromatin remodeling. These enzymes function by introducing temporary single-strand breaks (type I) or double-strand breaks (type II) into the phosphodiester backbone of DNA. This allows them to relax supercoils, untangle knots/catenanes formed during replication or repair processes, and ensure proper chromosome segregation. There are two main classes—Type I enzymes cleave one strand at a time without ATP hydrolysis; Type II cleave both strands using ATP energy. Human isoforms include TOP1/TOP2A/TOP2B; bacterial forms include gyrases which introduce negative supercoils. Because their activity is vital for rapidly dividing cells—and because their inhibition leads to lethal genome damage—DNA topoisomerases are validated therapeutic targets in cancer chemotherapy and antibacterial drug development.[1][2][4][5][6]

Other names

TopoisomeraseDNA topoisomerase IDNA topoisomerase IITopo ITopo IIGyrase (for bacterial type II)Reverse gyrase (archaeal)

– Inhibitors can stabilize the transient break in the DNA introduced by the enzyme, preventing religation and leading to accumulation of breaks that trigger cell death. – Some drugs act as poisons by trapping the enzyme-DNA cleavage complex; others inhibit catalytic activity or prevent binding to DNA.[6]