DNA Topoisomerase I (eukaryota)
SMART accession number:SM00435
Description: DNA Topoisomerase I (eukaryota), DNA topoisomerase V, Vaccina virus topoisomerase, Variola virus topoisomerase, Shope fibroma virus topoisomeras
Interpro abstract (IPR013499):

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; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (EC; 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 (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.

This entry represents the C-terminal region of DNA topoisomerase I enzymes from eukaryotes (type IB enzymes). This region covers both the catalytic core and the DNA-binding domains.

Human topoisomerase I has been shown to be inhibited by camptothecin (CPT), a plant alkaloid with antitumour activity [(PUBMED:1849260)]. 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 [(PUBMED:9488644)].

More information about this protein can be found at Protein of the Month: DNA Topoisomerase [].

GO process:DNA topological change (GO:0006265)
GO component:chromosome (GO:0005694)
GO function:DNA topoisomerase type I activity (GO:0003917), DNA binding (GO:0003677)
Family alignment:
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There are 274 TOPEUc domains in 274 proteins in SMART's nrdb database.

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