The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation.
The SET and transposase domain protein Metnase enhances chromosome decatenation: regulation by automethylation.
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DOI：
10.1093/nar/gkn560
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发表时间：
2008-10
影响因子：
14.9
通讯作者：
Hromas R
中科院分区：
文献类型：
--
作者：
Williamson EA;Rasila KK;Corwin LK;Wray J;Beck BD;Severns V;Mobarak C;Lee SH;Nickoloff JA;Hromas R
Metnase是一种人SET和转座酶结构域蛋白，其甲基化组蛋白H3并促进DNA双链断裂修复。我们现在表明，Metnase与拓扑异构酶IIα（Topo IIα），即关键的染色体脱连锁酶发生物理相互作用并共定位。Metnase通过去连环化促进进展，并增加对Topo IIα抑制剂ICRF-193和VP-16的耐药性。纯化的Metnase大大增强了Topo IIα对动基体DNA的脱连环作用，使其成为松弛的环状形式。含有Metnase的核提取物比不含Metnase的核提取物更快地使kDNA脱链，并且针对Metnase的中和抗血清逆转了脱链的增强。Metnase在K485处自动甲基化，甲基供体的存在阻断了Metnase对Topo IIα脱连环的增强，这意味着内部调节抑制。因此，Metnase增强Topo IIα脱连环化，并且该活性被自甲基化抑制。这些结果表明，癌细胞可以破坏Metnase介导对Topo IIα抑制剂的临床相关耐药性。
Metnase is a human SET and transposase domain protein that methylates histone H3 and promotes DNA double-strand break repair. We now show that Metnase physically interacts and co-localizes with Topoisomerase IIα (Topo IIα), the key chromosome decatenating enzyme. Metnase promotes progression through decatenation and increases resistance to the Topo IIα inhibitors ICRF-193 and VP-16. Purified Metnase greatly enhanced Topo IIα decatenation of kinetoplast DNA to relaxed circular forms. Nuclear extracts containing Metnase decatenated kDNA more rapidly than those without Metnase, and neutralizing anti-sera against Metnase reversed that enhancement of decatenation. Metnase automethylates at K485, and the presence of a methyl donor blocked the enhancement of Topo IIα decatenation by Metnase, implying an internal regulatory inhibition. Thus, Metnase enhances Topo IIα decatenation, and this activity is repressed by automethylation. These results suggest that cancer cells could subvert Metnase to mediate clinically relevant resistance to Topo IIα inhibitors.
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影响因子：
64.8
作者：
DOWNES, CS;CLARKE, DJ;JOHNSON, RT
通讯作者：
JOHNSON, RT
G9a的自甲基化及其对更广泛的底物特异性和HP1结合的影响。
影响因子：
14.9
作者：
Chin, Hang Gyeong;Esteve, Pierre-Olivier;Pradhan, Mihika;Benner, Jack;Patnaik, Debasis;Carey, Michael F;Pradhan, Sriharsa
通讯作者：
Pradhan, Sriharsa
DOI：
10.1083/jcb.200405167
发表时间：
2004-08-16
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mikhailov A;Shinohara M;Rieder CL
通讯作者：
Rieder CL
影响因子：
5.3
作者：
Liu, Danxu;Bischerour, Julien;Chalmers, Ronald
通讯作者：
Chalmers, Ronald
影响因子：
5.3
作者：
Miskey, Csaba;Papp, Balazs;Ivics, Zoltan
通讯作者：
Ivics, Zoltan