DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks [ PUBMED:7770916 ]. These enzymes have several functions: to remove … expand

DNA topoisomerases regulate the number of topological links between two DNA strands (i.e. change the number of superhelical turns) by catalysing transient single-or double-strand breaks, crossing the strands through one another, then resealing the breaks [ PUBMED:7770916 ]. These enzymes have several functions: to remove DNA supercoils during transcription and DNA replication; for strand breakage during recombination; for chromosome condensation; and to disentangle intertwined DNA during mitosis [ PUBMED:12042765 PUBMED:11395412 ]. DNA topoisomerases are divided into two classes: type I enzymes ( EC:5.6.2.2 ; topoisomerases I, III and V) break single-strand DNA, and type II enzymes ( EC:5.6.2.2 ; topoisomerases II, IV and VI) break double-strand DNA [ PUBMED:12596227 ].

Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (Topo IA; bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type IB (Topo IB; eukaryotic topoisomerase I and topoisomerase V). These enzymes are primarily responsible for relaxing positively and/or negatively supercoiled DNA, except for reverse gyrase, which can introduce positive supercoils into DNA. This function is vital for the processes of replication, transcription, and recombination. Unlike Topo IA enzymes, Topo IB enzymes do not require a single-stranded region of DNA or metal ions for their function. The type IB family of DNA topoisomerases includes eukaryotic nuclear topoisomerase I, topoisomerases of poxviruses, and bacterial versions of Topo IB [ PUBMED:17293019 ]. They belong to the superfamily of DNA breaking-rejoining enzymes, which share the same fold in their C-terminal catalytic domain and the overall reaction mechanism with tyrosine recombinases [ PUBMED:21087076 PUBMED:9488644 ]. The C-terminal catalytic domain in topoisomerases is linked to a divergent N-terminal domain that shows no sequence or structure similarity to the N-terminal domains of tyrosine recombinases [ PUBMED:20644584 PUBMED:17722649 ].

This entry describes domain 2 found in type IA topoisomerases, which may be an extension of the Toprim domain. The structures of bacterial topoisomerases I and III have been shown to consist of four domains that together form a toroidal structure with a central hole large enough to accommodate single- and double-stranded DNA. The N-terminal Toprim domain together with domain 3 forms the active site of the enzyme, while domains 2 and 4 form a single-strand DNA-binding groove [ PUBMED:14604525 PUBMED:10574789 ]. The Toprim domain ( IPR006171 ) forms a compact Rossmann fold that coordinates the Mg+2 ion [ PUBMED:9722641 ].