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研究揭示人类有丝分裂染色体的非线性力学
2022-05-08 16:05
来源：小柯机器人

荷兰阿姆斯特丹自由大学Gijs J. L. Wuite等研究人员合作揭示人类有丝分裂染色体的非线性力学。该项研究成果于2022年5月4日在线发表在《自然》杂志上。

研究人员报道了一个基于光学诱捕和操作的工作流程来研究人类染色体的组织。这允许在严格控制的实验条件下进行高分辨率的力测量和原生染色体的荧光可视化。研究人员用这种方法广泛地描述了染色体的力学和结构。值得注意的是，研究人员发现在不断增加的机械负荷下，染色体表现出非线性的僵化行为，与经典的聚合物模型所预测的不同。为了解释这种反常的僵化，研究人员引入了一个分层的蠕虫状链模型，将染色体描述为非线性蠕虫状链的异质性组合。
 
此外，通过拓扑异构酶IIα（TOP2A）在有丝分裂中的特异性诱导降解，研究人员提供证据表明TOP2A在保持染色体压实方面有作用。这里描述的方法为对正常和疾病相关的染色体的结构和动态进行广泛的调查打开了大门。
 
据介绍，在准备有丝分裂的细胞中，人类细胞的核DNA被压缩成独立的X形染色体。这种变形主要是由凝集素和TOP2A联合作用驱动的，一个多世纪以来人们一直用显微镜观察这种变形。然而，人们对有丝分裂染色体的结构组织知之甚少。
 
附：英文原文

Title: Nonlinear mechanics of human mitotic chromosomes

Author: Meijering, Anna E. C., Sarls, Kata, Nielsen, Christian F., Witt, Hannes, Harju, Janni, Kerklingh, Emma, Haasnoot, Guus H., Bizard, Anna H., Heller, Iddo, Broedersz, Chase P., Liu, Ying, Peterman, Erwin J. G., Hickson, Ian D., Wuite, Gijs J. L.

Issue&Volume: 2022-05-04

Abstract: In preparation for mitotic cell division, the nuclear DNA of human cells is compacted into individualized, X-shaped chromosomes1. This metamorphosis is driven mainly by the combined action of condensins and topoisomerase IIα (TOP2A)2,3, and has been observed using microscopy for over a century. Nevertheless, very little is known about the structural organization of a mitotic chromosome. Here we introduce a workflow to interrogate the organization of human chromosomes based on optical trapping and manipulation. This allows high-resolution force measurements and fluorescence visualization of native metaphase chromosomes to be conducted under tightly controlled experimental conditions. We have used this method to extensively characterize chromosome mechanics and structure. Notably, we find that under increasing mechanical load, chromosomes exhibit nonlinear stiffening behaviour, distinct from that predicted by classical polymer models4. To explain this anomalous stiffening, we introduce a hierarchical worm-like chain model that describes the chromosome as a heterogeneous assembly of nonlinear worm-like chains. Moreover, through inducible degradation of TOP2A5 specifically in mitosis, we provide evidence that TOP2A has a role in the preservation of chromosome compaction. The methods described here open the door to a wide array of investigations into the structure and dynamics of both normal and disease-associated chromosomes.

DOI: 10.1038/s41586-022-04666-5

Source: https://www.nature.com/articles/s41586-022-04666-5

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html


本期文章：《自然》：Online/在线发表

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