このエントリーをはてなブックマークに追加
ID 53139
FullText URL
Author
Onoda, Akihisa
Kiyama, Kazuko
Kimura, Hiroshi
Kawano, Shinji
Furuta, Ryohei
Tsutsui, Ken
Tsutsui, Kimiko M.
Abstract
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 II beta tagged with EGFP. Activity attenuation experiments and nuclear localization data reveal that the endogenous activity of topo II beta 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 II beta 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 II beta are mediated by the interplay between cellular RNA and the CRD.
Published Date
2014-07-17
Publication Title
Nucleic Acids Research
Volume
volume42
Issue
issue14
Publisher
Oxford University Press
Start Page
9005
End Page
9020
ISSN
0305-1048
Content Type
Journal Article
Related Url
http://ousar.lib.okayama-u.ac.jp/metadata/53130
language
英語
Copyright Holders
© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.
File Version
publisher
Refereed
True
DOI
Web of Science KeyUT