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通过中期赤道带 Aurora B 梯度对染色体分离的反馈控制。

Feedback control of chromosome separation by a midzone Aurora B gradient.

机构信息

Chromosome Instability and Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal.

Center for Mathematics, Universidade do Porto, Rua do Campo Alegre 687, 4169-007 Porto, Portugal.

出版信息

Science. 2014 Jul 18;345(6194):332-336. doi: 10.1126/science.1251121. Epub 2014 Jun 12.

DOI:10.1126/science.1251121
PMID:24925910
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5240038/
Abstract

Accurate chromosome segregation during mitosis requires the physical separation of sister chromatids before nuclear envelope reassembly (NER). However, how these two processes are coordinated remains unknown. Here, we identified a conserved feedback control mechanism that delays chromosome decondensation and NER in response to incomplete chromosome separation during anaphase. A midzone-associated Aurora B gradient was found to monitor chromosome position along the division axis and to prevent premature chromosome decondensation by retaining Condensin I. PP1/PP2A phosphatases counteracted this gradient and promoted chromosome decondensation and NER. Thus, an Aurora B gradient appears to mediate a surveillance mechanism that prevents chromosome decondensation and NER until effective separation of sister chromatids is achieved. This allows the correction and reintegration of lagging chromosomes in the main nuclei before completion of NER.

摘要

在有丝分裂过程中,准确的染色体分离需要在核膜重新组装(NER)之前将姐妹染色单体物理分离。然而,这两个过程是如何协调的仍然未知。在这里,我们发现了一种保守的反馈控制机制,该机制可以延迟染色体解凝聚和 NER,以响应后期姐妹染色单体分离不完全。发现一个位于中部的 Aurora B 梯度可以沿分裂轴监测染色体位置,并通过保留凝聚素 I 来防止过早的染色体解凝聚。PP1/PP2A 磷酸酶拮抗这种梯度,并促进染色体解凝聚和 NER。因此,Aurora B 梯度似乎介导了一种监控机制,该机制可以防止染色体解凝聚和 NER,直到实现姐妹染色单体的有效分离。这使得滞后染色体在 NER 完成之前可以在主核中得到纠正和重新整合。

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本文引用的文献

1
Aurora B defines its own chromosomal targeting by opposing the recruitment of the phosphatase scaffold Repo-Man.极光 B 通过拮抗磷酸酶支架 Repo-Man 的募集来定义其自身的染色体靶向。
Curr Biol. 2013 Jun 17;23(12):1136-43. doi: 10.1016/j.cub.2013.05.017. Epub 2013 Jun 6.
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DNA breaks and chromosome pulverization from errors in mitosis.有丝分裂错误导致的 DNA 断裂和染色体粉碎。
Nature. 2012 Jan 18;482(7383):53-8. doi: 10.1038/nature10802.
3
Chromosome segregation errors as a cause of DNA damage and structural chromosome aberrations.染色体分离错误导致 DNA 损伤和结构染色体异常。
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Repo-Man coordinates chromosomal reorganization with nuclear envelope reassembly during mitotic exit.Repo-Man 在有丝分裂末期协调染色体重排与核膜重组。
Dev Cell. 2011 Aug 16;21(2):328-42. doi: 10.1016/j.devcel.2011.06.020. Epub 2011 Aug 4.
5
Condensin association with histone H2A shapes mitotic chromosomes.凝聚素与组蛋白 H2A 缔合形成有丝分裂染色体。
Nature. 2011 Jun 1;474(7352):477-83. doi: 10.1038/nature10179.
6
Condensin phosphorylated by the Aurora-B-like kinase Ark1 is continuously required until telophase in a mode distinct from Top2.由 Aurora-B 样激酶 Ark1 磷酸化的凝聚素在末期之前以不同于 Top2 的模式持续需要。
J Cell Sci. 2011 Jun 1;124(Pt 11):1795-807. doi: 10.1242/jcs.078733. Epub 2011 May 3.
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A midzone-based ruler adjusts chromosome compaction to anaphase spindle length.基于中带的标尺将染色体的压缩调整到后期纺锤体的长度。
Science. 2011 Apr 22;332(6028):465-8. doi: 10.1126/science.1201578. Epub 2011 Mar 10.
8
Binucleine 2, an isoform-specific inhibitor of Drosophila Aurora B kinase, provides insights into the mechanism of cytokinesis.双体素 2,果蝇 Aurora B 激酶的同工型特异性抑制剂,为细胞分裂机制提供了新的见解。
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Live-cell imaging RNAi screen identifies PP2A-B55alpha and importin-beta1 as key mitotic exit regulators in human cells.活细胞成像 RNAi 筛选鉴定出 PP2A-B55alpha 和 importin-beta1 是人细胞有丝分裂退出的关键调节因子。
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Curr Biol. 2009 Apr 14;19(7):607-12. doi: 10.1016/j.cub.2009.02.046. Epub 2009 Mar 19.