<p>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 [<cite idref="PUB00005437"/>]. 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 [<cite idref="PUB00020794"/>, <cite idref="PUB00016842"/>]. DNA topoisomerases are divided into two classes: type I enzymes (<db_xref db="EC" dbkey="5.99.1.2"/>; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (<db_xref db="EC" dbkey="5.99.1.3"/>; topoisomerases II, IV and VI) break double-strand DNA [<cite idref="PUB00020793"/>].</p><p>Type I topoisomerases are ATP-independent enzymes (except for reverse gyrase), and can be subdivided according to their structure and reaction mechanisms: type IA (bacterial and archaeal topoisomerase I, topoisomerase III and reverse gyrase) and type 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. </p><p> This entry describes topoisomerase I from bacteria, which is more closely related to archaeal than to eukaryotic topoisomerase I [<cite idref="PUB00016766"/>]. Topoisomerase I is the major enzyme for relaxing negatively supercoiled DNA, and its presence is balanced by reverse gyrase, which can introduce negative supercoils. Prokaryotic topoisomerase I folds in an unusual way to give 4 distinct domains, enclosing a hole large enough to accommodate a double-stranded DNA segment. A tyrosine at the active site, which lies at the interface of 2 domains, is involved in transient breakage of a DNA strand, and the formation of a covalent protein-DNA intermediate through a 5'-phosphotyrosine linkage. The structure reveals a plausible mechanism by which this and related enzymes could catalyse the passage of one DNA strand through a transient break in another strand [<cite idref="PUB00020796"/>]. Topoisomerase I require Mg2+ as a cofactor for catalysis to take place. </p><p>More information about this protein can be found at Protein of the Month: DNA Topoisomerase [<cite idref="PUB00035961"/>].</p>