Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha.
Chromosome breakage is regulated by the interaction of the BLM helicase and topoisomerase IIalpha.
复制标题
染色体断裂由 BLM 解旋酶和拓扑异构酶 IIα 的相互作用调节。
DOI：
10.1158/0008-5472.can-10-1727
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发表时间：
2011
期刊：
影响因子：
11.2
通讯作者：
Groden,Joanna
中科院分区：
文献类型：
--
作者：
Russell,Beatriz;Bhattacharyya,Saumitri;Keirsey,Jeremy;Sandy,April;Grierson,Patrick;Perchiniak,Erin;Kavecansky,Juraj;Acharya,Samir;Groden,Joanna
缺乏RecQ样解旋酶BLM的细胞以染色体变化为特征，这些变化表明分解重组中间产物和维持染色体稳定所需的正常机制被破坏。人BLm和拓扑异构酶IIα通过BLM第489-587位氨基酸直接相互作用，并主要在细胞周期的G2和M期晚期共存。根据对代表某些重组中间产物的特定底物的分析，该区域的缺失不影响博莱曼固有的玻璃螺旋酶活性，但抑制拓扑异构酶IIα依赖的活性增强。从BLM中删除相互作用结构域不能纠正转基因BLM缺陷细胞的染色体断裂。我们的结果表明，博莱姆-拓扑异构酶II的α相互作用对于防止染色体断裂和阐明DNA修复机制是重要的，而DNA修复机制对于维持细胞中染色体的稳定性和防止肿瘤形成至关重要。©2011 AACR。
Cells deficient in the recQ-like helicase BLM are characterized by chromosome changes that suggest the disruption of normal mechanisms needed to resolve recombination intermediates and to maintain chromosome stability. Human BLM and topoisomerase IIα interact directly via amino acids 489–587 of BLM and colocalize predominantly in late G2and M phases of the cell cycle. Deletion of this region does not affect the inherentin vitrohelicase activity of BLM but inhibits the topoisomerase IIα–dependent enhancement of its activity, based on the analysis of specific DNA substrates that represent some recombination intermediates. Deletion of the interaction domain from BLM fails to correct the elevated chromosome breakage of transfected BLM-deficient cells. Our results demonstrate that the BLM–topoisomerase IIα interaction is important for preventing chromosome breakage and elucidate a DNA repair mechanism that is critical to maintain chromosome stability in cells and to prevent tumor formation.Cancer Res; 71(2); 561–71. ©2011 AACR.