topoisomerase

Topoisomerases are enzymes that regulate DNA topology by creating transient breaks in the DNA backbone to relieve supercoiling and disentangle DNA during essential cellular processes, including replication, transcription, recombination, and chromosome segregation. By altering the linking number of DNA, these enzymes help maintain genome integrity and facilitate passage of one DNA strand through another.

There are two main types: type I and type II. Type I enzymes cleave a single strand of DNA and adjust the linking number by one, typically without direct ATP hydrolysis. Type II enzymes cut both strands, change the linking number by two, and generally require ATP. Mechanistically, Type I relies on a catalytic tyrosine that forms a transient covalent bond with the DNA and religates after passage or rotation of the DNA strand; Type II creates a transient double-strand break, passes another duplex through the break, and then religates, driven by ATP-dependent conformational changes. Type I are often monomeric or dimeric; Type II are usually multimeric holoenzymes.

In bacteria, DNA gyrase (a type II enzyme) introduces negative supercoils, while Topo IV decatenates daughter chromosomes after replication. Eukaryotes encode Topo I and Topo II, with Topo II also involved in chromosome condensation and decatenation. Topoisomerases are targets for drugs: camptothecin and its derivatives inhibit Topo I; etoposide and doxorubicin inhibit Topo II; fluoroquinolones inhibit bacterial gyrase and Topo IV. In research, topoisomerases are used to study DNA topology and to manipulate DNA in vitro.