<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 represents the C-terminal region of DNA topoisomerase I enzymes, including both type IA enzymes from bacteria and type IB enzymes from eukaryotes and viruses. This region covers both the catalytic core and the DNA-binding domains.</p><p>Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity [<cite idref="PUB00004398"/>]. The crystal structures of human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps" around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin has been proposed on the basis of chemical and biochemical information combined with the three-dimensional structures of topoisomerase I-DNA complexes [<cite idref="PUB00005230"/>].</p><p> <taxon tax_id="10245">Vaccinia virus</taxon>, a cytoplasmically-replicating poxvirus, encodes a type I DNA topoisomerase that is biochemically similar to eukaryotic-like DNA topoisomerases I, and which has been widely studied as a model topoisomerase. It is the smallest topoisomerase known and is unusual in that it is resistant to the potent chemotherapeutic agent camptothecin. The crystal structure of an amino-terminal fragment of vaccinia virus DNA topoisomerase I shows that the fragment forms a five-stranded, antiparallel beta-sheet with two short alpha-helices and connecting loops. Residues that are conserved between all eukaryotic-like type I topoisomerases are not clustered in particular regions of the structure [<cite idref="PUB00006312"/>]. </p><p>More information about this protein can be found at Protein of the Month: DNA Topoisomerase [<cite idref="PUB00035961"/>].</p>