TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution.

TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution.
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DOI:
10.1038/ncomms7572
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发表时间:
2015-03-12
影响因子:
16.6
通讯作者:
Niedzwiedz, Wojciech
Niedzwiedz, Wojciech
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Broderick, Ronan;Nieminuszczy, Jadwiga;Blackford, Andrew N.;Winczura, Alicja;Niedzwiedz, Wojciech

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在有丝分裂过程中,姐妹染色单体必须被忠实地分离,以确保子细胞接受每条染色体的一个拷贝。然而,在复制之后,它们经常保持纠缠。拓扑异构酶IIα(TOP 2A)已被提出来解决这种纠缠,但TOP 2A招募这些结构的机制仍然知之甚少。在这里,我们确定TOPBP 1作为一个新的相互作用的TOP 2A,并揭示它是所需的TOP 2A招聘到超细后期桥(UFB)在有丝分裂。TOPBP 1的C-末端区域与TOP 2A相互作用,并且TOPBP 1向UFB的募集需要其BRCT结构域5。TOPBP 1的缺失导致UFB的积累,其中大部分来自着丝粒基因座。因此,在TOP 2A结合方面有缺陷的TOPBP 1突变体的表达引起TOP 2A耗竭。这些发现为TOP 2A如何在有丝分裂过程中促进UFB的分解提供了新的机制见解,并强调了TOPBP 1在这一过程中的关键作用。
During mitosis, sister chromatids must be faithfully segregated to ensure that daughter cells receive one copy of each chromosome. However, following replication they often remain entangled. Topoisomerase IIα (TOP2A) has been proposed to resolve such entanglements, but the mechanisms governing TOP2A recruitment to these structures remain poorly understood. Here, we identify TOPBP1 as a novel interactor of TOP2A, and reveal that it is required for TOP2A recruitment to ultra-fine anaphase bridges (UFBs) in mitosis. The C-terminal region of TOPBP1 interacts with TOP2A, and TOPBP1 recruitment to UFBs requires its BRCT domain 5. Depletion of TOPBP1 leads to accumulation of UFBs, the majority of which arise from centromeric loci. Accordingly, expression of a TOPBP1 mutant that is defective in TOP2A binding phenocopies TOP2A depletion. These findings provide new mechanistic insights into how TOP2A promotes resolution of UFBs during mitosis, and highlights a pivotal role for TOPBP1 in this process.
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