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《细胞周期中动粒结构的动态全景百科全书》

CENcyclopedia: Dynamic Landscape of Kinetochore Architecture Throughout the Cell Cycle.

作者信息

Chen Yu-Chia, Kilic Ece, Wang Evelyn, Rossman Will, Suzuki Aussie

机构信息

McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Madison, Wisconsin, USA.

Molecular Cellular Pharmacology Graduate Program, University of Wisconsin-Madison, Madison, Wisconsin, USA.

出版信息

bioRxiv. 2024 Dec 5:2024.12.05.627000. doi: 10.1101/2024.12.05.627000.

DOI:10.1101/2024.12.05.627000
PMID:39677682
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11643120/
Abstract

The kinetochore, an intricate macromolecular protein complex located on chromosomes, plays a pivotal role in orchestrating chromosome segregation. It functions as a versatile platform for microtubule assembly, diligently monitors microtubule binding fidelity, and acts as a force coupler. Comprising over 100 distinct proteins, many of which exist in multiple copies, the kinetochore's composition dynamically changes throughout the cell cycle, responding to specific timing and conditions. This dynamicity is important for establishing functional kinetochores, yet the regulatory mechanisms of these dynamics have largely remained elusive. In this study, we employed advanced quantitative immunofluorescence techniques to meticulously chart the dynamics of kinetochore protein levels across the cell cycle. These findings offer a comprehensive view of the dynamic landscape of kinetochore architecture, shedding light on the detailed mechanisms of microtubule interaction and the nuanced characteristics of kinetochore proteins. This study significantly advances our understanding of the molecular coordination underlying chromosome segregation.

摘要

动粒是位于染色体上的一种复杂的大分子蛋白质复合体,在协调染色体分离过程中起着关键作用。它作为微管组装的通用平台,勤勉地监测微管结合的保真度,并充当力耦合器。动粒由100多种不同的蛋白质组成,其中许多以多个拷贝存在,其组成在整个细胞周期中动态变化,以响应特定的时间和条件。这种动态性对于建立功能性动粒很重要,然而这些动态变化的调控机制在很大程度上仍然难以捉摸。在这项研究中,我们采用先进的定量免疫荧光技术,精心绘制了整个细胞周期中动粒蛋白水平的动态变化。这些发现提供了动粒结构动态景观的全面视图,揭示了微管相互作用的详细机制以及动粒蛋白的细微特征。这项研究显著推进了我们对染色体分离背后分子协调的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/f73f0536f7ae/nihpp-2024.12.05.627000v1-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/44ee53967c4e/nihpp-2024.12.05.627000v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/19462cfd3dfb/nihpp-2024.12.05.627000v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/30c865c68414/nihpp-2024.12.05.627000v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/93378c13a3b0/nihpp-2024.12.05.627000v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/f8708fdeaa88/nihpp-2024.12.05.627000v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/e5f3bb31fd17/nihpp-2024.12.05.627000v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/34eee2f5f3fd/nihpp-2024.12.05.627000v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/ebf3179e8d60/nihpp-2024.12.05.627000v1-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/f73f0536f7ae/nihpp-2024.12.05.627000v1-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/44ee53967c4e/nihpp-2024.12.05.627000v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/19462cfd3dfb/nihpp-2024.12.05.627000v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/30c865c68414/nihpp-2024.12.05.627000v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/93378c13a3b0/nihpp-2024.12.05.627000v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/f8708fdeaa88/nihpp-2024.12.05.627000v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/e5f3bb31fd17/nihpp-2024.12.05.627000v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/34eee2f5f3fd/nihpp-2024.12.05.627000v1-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/ebf3179e8d60/nihpp-2024.12.05.627000v1-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5ed/11643120/f73f0536f7ae/nihpp-2024.12.05.627000v1-f0009.jpg

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本文引用的文献

1
ImmunoCellCycle-ID - a high-precision immunofluorescence-based method for cell cycle identification.免疫细胞周期鉴定法(ImmunoCellCycle-ID)——一种基于免疫荧光的高精度细胞周期鉴定方法。
J Cell Sci. 2024 Nov 15;137(22). doi: 10.1242/jcs.263414. Epub 2024 Nov 20.
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Structure of the human KMN complex and implications for regulation of its assembly.人类 KMN 复合物的结构及其对其组装调节的影响。
Nat Struct Mol Biol. 2024 Jun;31(6):861-873. doi: 10.1038/s41594-024-01230-9. Epub 2024 Mar 8.
3
Structure of the human outer kinetochore KMN network complex.
人类外中心体 KMN 网络复合物的结构。
Nat Struct Mol Biol. 2024 Jun;31(6):874-883. doi: 10.1038/s41594-024-01249-y. Epub 2024 Mar 8.
4
PLK1 phosphorylation of ZW10 guides accurate chromosome segregation in mitosis.PLK1 对 ZW10 的磷酸化作用指导有丝分裂中染色体的准确分离。
J Mol Cell Biol. 2024 Jul 29;16(2). doi: 10.1093/jmcb/mjae008.
5
RZZ-Spindly and CENP-E form an integrated platform to recruit dynein to the kinetochore corona.RZZ-纺锤体和 CENP-E 形成一个整合平台,将动力蛋白招募到动粒冠。
EMBO J. 2023 Dec 11;42(24):e114838. doi: 10.15252/embj.2023114838. Epub 2023 Nov 20.
6
A bifunctional kinase-phosphatase module balances mitotic checkpoint strength and kinetochore-microtubule attachment stability.一个双功能激酶-磷酸酶模块平衡了有丝分裂检查点的强度和着丝粒-微管连接的稳定性。
EMBO J. 2023 Oct 16;42(20):e112630. doi: 10.15252/embj.2022112630. Epub 2023 Sep 15.
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Juxtaposition of Bub1 and Cdc20 on phosphorylated Mad1 during catalytic mitotic checkpoint complex assembly.在催化有丝分裂检查点复合物组装过程中,Bub1 和 Cdc20 与磷酸化 Mad1 并列。
Nat Commun. 2022 Oct 26;13(1):6381. doi: 10.1038/s41467-022-34058-2.
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Structural insights into human CCAN complex assembled onto DNA.对组装在DNA上的人类CCAN复合物的结构见解。
Cell Discov. 2022 Sep 9;8(1):90. doi: 10.1038/s41421-022-00439-6.
9
Dynamic cell cycle-dependent phosphorylation modulates CENP-L-CENP-N centromere recruitment.动态细胞周期依赖性磷酸化调节着着丝粒蛋白 L-着丝粒蛋白 N 向着丝粒的募集。
Mol Biol Cell. 2022 Sep 1;33(10):ar87. doi: 10.1091/mbc.E22-06-0239. Epub 2022 Jul 13.
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Mol Cell. 2022 Jun 2;82(11):2113-2131.e8. doi: 10.1016/j.molcel.2022.04.027. Epub 2022 May 6.