Assembly of nuclear matrix-bound protein complexes involved in non-homologous end joining is induced by inhibition of DNA topoisomerase II.

Kantidze OL; Iarovaia OV; Razin SV

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Assembly of nuclear matrix-bound protein complexes involved in non-homologous end joining is induced by inhibition of DNA topoisomerase II.

机译：组装核matrix-bound蛋白复合物参与异源端加入诱导通过抑制DNA拓扑异构酶II。

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Topoisomerases maintain the DNA structure by relieving the torsional stress and alleviating other topological problems occurring in DNA during transcription and replication. Topoisomerase II appears to have a close association with the family of proteins involved in the organization of chromatin in a series of loops on the proteinaceous chromosomal matrix. Beyond its physiological functions, topoisomerase II is the target for some of the most active anticancer drugs. Inhibition of the topoisomerase II function can result in DNA double-strand breaks (DSBs) and, thus, lead to chromosomal translocations. The earliest event during DSB repair is phosphorylation of histone H2AX at S139 (so-called gammaH2AX) which is believed to serve as a focal point for the assembly of repair proteins at the DSB. In this work, we have demonstrated the formation of gammaH2AX foci in two human cell lines--K562 and HeLa--after suppression of topoisomerase II activity with etoposide. Furthermore, these foci remained visible at nuclear matrices and colocalized with the major components of non-homologous end joining (NHEJ) system of DSBs repair. Thus, inhibition of topoisomerase II activity triggers assembly of NHEJ complexes at the nuclear matrix.

机译：拓扑异构酶维持DNA结构缓解扭转应力和缓解其他拓扑问题发生在DNA在转录和复制。拓扑异构酶ⅱ似乎已经结束与蛋白质家族在一系列的染色质的组织循环在蛋白质的染色体矩阵。超出其生理功能、拓扑异构酶二是一些最活跃的目标抗癌药物。二世函数会导致DNA双链断裂(双边带),从而导致染色体易位。修复是组蛋白的磷酸化H2AX S139(所谓gammaH2AX)服务作为大会的焦点的修复蛋白质在争端解决机构。证明gammaH2AX疫源地的形成两个人类细胞系K562和海拉抑制拓扑异构酶ⅱ的活动依托泊苷。在核矩阵和与可见异源的主要组件加入(NHEJ)的双边带系统修复。抑制拓扑异构酶II活动触发NHEJ复合物的组装核矩阵。

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《Journal of Cellular Physiology》 |2006年第3期|660-667|共8页
作者
Kantidze OL; Iarovaia OV; Razin SV;
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作者单位

Laboratory of Structural and Functional Organization of Chromosomes, Institute of Gene Biology RAS, Moscow, Russia.;

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原文格式 PDF
正文语种英语
中图分类细胞生物学;
关键词
Type II DNA Topoisomerase; DNA Topoisomerases; Non-Homologous DNA End-JoiningNitric Oxide Synthase 2ANuclear MatrixDNA structureNuclear Matrix-Associated ProteinsH2AX protein, human;

机译：II型DNA拓扑异构酶;DNADNA拓扑异构酶;异源End-JoiningNitric氧化合成酶2无核的MatrixDNA structureNuclear矩阵ProteinsH2AX蛋白质,人类;

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Assembly of nuclear matrix-bound protein complexes involved in non-homologous end joining is induced by inhibition of DNA topoisomerase II.

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