InterPro domain: IPR004085

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 [ 1 ]. 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 [ 2 , 3 ]. DNA topoisomerases are divided into two classes: type I enzymes ( 5.99.1.2 ; topoisomerases I, III and V) break single-strand DNA, and type II enzymes ( 5.99.1.3 ; topoisomerases II, IV and VI) break double-strand DNA [ 4 ].

Type II topoisomerases are ATP-dependent enzymes, and can be subdivided according to their structure and reaction mechanisms: type IIA (topoisomerase II or gyrase, and topoisomerase IV) and type IIB (topoisomerase VI). These enzymes are responsible for relaxing supercoiled DNA as well as for introducing both negative and positive supercoils [ 5 ].

This entry represents subunit A of topoisomerase VI, a type IIB topoisomerase found predominantly in archaea, but also in a few eukayotes, such as the plant Arabidopsis thaliana [ 6 ]. This enzyme assembles as a heterotetramer, consisting of two A subunits required for DNA cleavage and two B subunits required for ATP hydrolysis. The B subunit is structurally similar to the ATPase domain of type IIA topoisomerases, but the A subunit is distinct, and instead shares homology with the Spo11 protein that mediates double-strand DNA breaks during meiotic recombination in eukaryotes [ 7 ]. The core of subunit A is a dimer, with a deep groove in which the DNA molecule is thought to bind, with the monomers separating during DNA transport. Therefore, though related to type IIA topoisomerases, topoisomerase VI may have a distinctive mechanism of action.

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2. Cellular roles of DNA topoisomerases: a molecular perspective. Nat. Rev. Mol. Cell Biol. 3, 430-40
3. DNA topoisomerases: structure, function, and mechanism. Annu. Rev. Biochem. 70, 369-413
4. Phylogenomics of type II DNA topoisomerases. Bioessays 25, 232-42
5. Structure and function of type II DNA topoisomerases. Biochem. J. 303 ( Pt 3), 681-95
6. Emerging roles for plant topoisomerase VI. Chem. Biol. 10, 107-11
7. Structure and function of an archaeal topoisomerase VI subunit with homology to the meiotic recombination factor Spo11. EMBO J. 18, 6177-88