Nuclear dynamics of topoisomerase IIβ reflects its catalytic activity that is regulated by binding of RNA to the C-terminal domain.
Nuclear dynamics of topoisomerase IIβ reflects its catalytic activity that is regulated by binding of RNA to the C-terminal domain.
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DOI：
10.1093/nar/gku640
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发表时间：
2014-08
影响因子：
14.9
通讯作者：
Tsutsui KM
中科院分区：
文献类型：
--
作者：
Onoda A;Hosoya O;Sano K;Kiyama K;Kimura H;Kawano S;Furuta R;Miyaji M;Tsutsui K;Tsutsui KM
DNA 拓扑异构酶 II (topo II) 通过切割/重新连接循环改变 DNA 拓扑结构，从而有助于各种核 DNA 处理。目前尚不清楚这种酶在核环境中是如何被控制的。多项研究表明，其 C 末端结构域 (CTD) 对于基础松弛活性是必不可少的，具有一定的调节影响。在这项工作中，我们研究了核定位对原子核活动调节的影响。具体来说，人类细胞用带有 EGFP 标记的野生型和突变型拓扑 IIβ 转染。活性衰减实验和核定位数据表明，topo IIβ的内源活性与其亚核分布相关。酶在核质中的活性形式和核仁中的静止形式之间以动态平衡方式穿梭。从机制上讲，该过程涉及与 RNA 的束缚事件。分离的 RNA 通过与 CTD（称为 CRD）的特定 50 个残基区域相互作用，在体外抑制拓扑 IIβ 的催化活性。综上所述，这些结果表明拓扑 IIβ 的亚核分布和活性调节都是由细胞 RNA 和 CRD 之间的相互作用介导的。
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 IIβ tagged with EGFP. Activity attenuation experiments and nuclear localization data reveal that the endogenous activity of topo IIβ 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 IIβ 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 IIβ are mediated by the interplay between cellular RNA and the CRD.
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DOI：
10.1083/jcb.153.7.1341
发表时间：
2001-06-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kimura H;Cook PR
通讯作者：
Cook PR
影响因子：
14.9
作者：
Cole C;Barber JD;Barton GJ
通讯作者：
Barton GJ
拓扑异构酶iialpha和IIBETA的C末端区域确定体内酶的同工型特异性功能。
影响因子：
14.9
作者：
Linka, Rene M;Porter, Andrew C G;Volkov, Arsen;Mielke, Christian;Boege, Fritz;Christensen, Morten O
通讯作者：
Christensen, Morten O
影响因子：
3.7
作者：
Mirski, SEL;Gerlach, JH;Cole, SPC
通讯作者：
Cole, SPC
影响因子：
64.8
作者：
Dong, Ken C.;Berger, James M.
通讯作者：
Berger, James M.