Structural highlights
Function
[TOP2A_HUMAN] Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes.[1]
Evolutionary Conservation
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Publication Abstract from PubMed
Type IIA DNA topoisomerases play multiple essential roles in the management of higher-order DNA structure, including modulation of topological state, chromosome segregation, and chromatin condensation. These diverse physiologic functions are all accomplished through a common molecular mechanism, wherein the protein catalyzes transient cleavage of a DNA duplex (the G-segment) to yield a double-stranded gap through which another duplex (the T-segment) is passed. The overall process is orchestrated by the opening and closing of molecular "gates" in the topoisomerase structure, which is regulated by ATP binding, hydrolysis, and release of ADP and inorganic phosphate. Here we present two crystal structures of the ATPase domain of human DNA topoisomerase IIalpha in different nucleotide-bound states. Comparison of these structures revealed rigid-body movement of the structural modules within the ATPase domain, suggestive of the motions of a molecular gate.
Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase.,Wei H, Ruthenburg AJ, Bechis SK, Verdine GL J Biol Chem. 2005 Nov 4;280(44):37041-7. Epub 2005 Aug 12. PMID:16100112[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lee S, Jung SR, Heo K, Byl JA, Deweese JE, Osheroff N, Hohng S. DNA cleavage and opening reactions of human topoisomerase IIalpha are regulated via Mg2+-mediated dynamic bending of gate-DNA. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):2925-30. doi:, 10.1073/pnas.1115704109. Epub 2012 Feb 9. PMID:22323612 doi:http://dx.doi.org/10.1073/pnas.1115704109
- ↑ Wei H, Ruthenburg AJ, Bechis SK, Verdine GL. Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase. J Biol Chem. 2005 Nov 4;280(44):37041-7. Epub 2005 Aug 12. PMID:16100112 doi:10.1074/jbc.M506520200
