Domain

DNA topoisomerase I, eukaryotic-type (IPR013499)

Short name: TopoI_euk

Domain relationships

None.

Description

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 [PMID: 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 [PMID: 12042765, PMID: 11395412]. DNA topoisomerases are divided into two classes: type I enzymes (EC:5.99.1.2; topoisomerases I, III and V) break single-strand DNA, and type II enzymes (EC:5.99.1.3; topoisomerases II, IV and VI) break double-strand DNA [PMID: 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 [PMID: 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 [PMID: 9488644].

GO terms

Biological Process

GO:0006265 DNA topological change

Molecular Function

GO:0003677 DNA binding
GO:0003917 DNA topoisomerase type I activity

Cellular Component

GO:0005694 chromosome

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
SMART