首页> 外文学位 >The extreme C-terminus of human Topoisomerase II alpha defines a novel bi-modular DNA tether essential for the formation of mitotic chromosomes.
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The extreme C-terminus of human Topoisomerase II alpha defines a novel bi-modular DNA tether essential for the formation of mitotic chromosomes.

机译:人类拓扑异构酶IIα的极端C末端定义了一种新型的双模块DNA系链,对形成有丝分裂染色体至关重要。

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摘要

Topoisomerase II is the target of an important class of anti-cancer drugs, but tumor cells can become resistant by reducing the association of the enzyme with chromosomes. We have determined the mechanism of Topo IIα recruitment to chromatin and provide new insight into the formation of mitotic chromosomes. We describe the first example of what is likely to be a widespread mechanism for recruitment of chromosomal proteins involving a bi-modular element consisting of an NLS and an associated DNA tether. Catalytically dead Topo IIα is successfully targeted to chromatin, but both the catalytic activity and the bi-modular targeting element are essential for mitotic chromosome formation. Because reduced strand passage activity protects cells from Topo IIα-targeted drugs, it is likely that mutations in the bi-modular element would lead to drug-resistance.
机译:拓扑异构酶II是一类重要的抗癌药物的靶标,但肿瘤细胞可通过减少该酶与染色体的结合而变得具有抗性。我们已经确定了TopoIIα募集到染色质的机制,并为有丝分裂染色体的形成提供了新的见识。我们描述的第一个示例可能是涉及包含NLS和相关DNA系链的双模块元件的染色体蛋白募集的广泛机制。催化死亡的TopoIIα已成功靶向染色质,但是催化活性和双模块靶向元件对于有丝分裂染色体的形成都是必不可少的。由于降低的链传递活性可保护细胞免受针对TopoIIα的药物的侵害,因此双模块元件中的突变很可能导致耐药性。

著录项

  • 作者

    Lane, Andrew Besancon.;

  • 作者单位

    University of Minnesota.;

  • 授予单位 University of Minnesota.;
  • 学科 Biology Molecular.;Biology Cell.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 109 p.
  • 总页数 109
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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