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Nuclear dynamics of topoisomerase IIß reflects its catalytic activity that is regulated by binding of RNA to the C-terminal domain.

Authors: Onoda, Akihisa  Hosoya, Osamu  Sano, Kuniaki  Kiyama, Kazuko  Kimura, Hiroshi  Kawano, Shinji  Furuta, Ryohei  Miyaji, Mary  Tsutsui, Ken  Tsutsui, Kimiko M 
Citation: Onoda A, etal., Nucleic Acids Res. 2014 Aug;42(14):9005-20. doi: 10.1093/nar/gku640. Epub 2014 Jul 17.
Pubmed: (View Article at PubMed) PMID:25034690
DOI: Full-text: DOI:10.1093/nar/gku640

DNA topoisomerase II (topo II) changes DNA topology by cleavage/re-ligation cycle(s) and thus contributes to various nuclear DNA transactions. It is largely unknown how the enzyme is controlled in a nuclear context. Several studies have suggested that its C-terminal domain (CTD), which is dispensable for basal relaxation activity, has some regulatory influence. In this work, we examined the impact of nuclear localization on regulation of activity in nuclei. Specifically, human cells were transfected with wild-type and mutant topo IIß tagged with EGFP. Activity attenuation experiments and nuclear localization data reveal that the endogenous activity of topo IIß is correlated with its subnuclear distribution. The enzyme shuttles between an active form in the nucleoplasm and a quiescent form in the nucleolus in a dynamic equilibrium. Mechanistically, the process involves a tethering event with RNA. Isolated RNA inhibits the catalytic activity of topo IIß in vitro through the interaction with a specific 50-residue region of the CTD (termed the CRD). Taken together, these results suggest that both the subnuclear distribution and activity regulation of topo IIß are mediated by the interplay between cellular RNA and the CRD.

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CRRD Object Information
CRRD ID: 13432146
Created: 2017-09-21
Species: All species
Last Modified: 2017-09-21
Status: ACTIVE



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