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有丝分裂染色体的桥连介导压缩

Bridging-mediated compaction of mitotic chromosomes.

作者信息

Forte Giada, Boteva Lora, Gilbert Nick, Cook Peter R, Marenduzzo Davide

机构信息

SUPA, School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.

出版信息

Nucleus. 2025 Dec;16(1):2497765. doi: 10.1080/19491034.2025.2497765. Epub 2025 May 9.

Abstract

Within living cells, chromosome shapes undergo a striking morphological transition, from loose and uncondensed fibers during interphase to compacted and cylindrical structures during mitosis. ATP driven loop extrusion performed by a specialized protein complex, condensin, has recently emerged as a key driver of this transition. However, while this mechanism can successfully recapitulate the compaction of chromatids during the early stages of mitosis, it cannot capture structures observed after prophase. Here we hypothesize that a condensin bridging activity plays an additional important role, and review evidence - obtained largely through molecular dynamics simulations - that, in combination with loop extrusion, it can generate compact metaphase cylinders. Additionally, the resulting model qualitatively explains the unusual elastic properties of mitotic chromosomes observed in micromanipulation experiments and provides insights into the role of condensins in the formation of abnormal chromosome structures associated with common fragile sites.

摘要

在活细胞内,染色体形态会经历显著的转变,从间期松散且未浓缩的纤维状态,转变为有丝分裂期间紧密的圆柱状结构。由一种特殊的蛋白质复合体凝缩蛋白执行的ATP驱动的环状挤压,最近已成为这种转变的关键驱动因素。然而,虽然这种机制能够成功再现有丝分裂早期染色单体的压缩过程,但它无法捕捉到前期之后观察到的结构。在此,我们假设凝缩蛋白的桥接活性发挥着额外的重要作用,并回顾了主要通过分子动力学模拟获得的证据,即与环状挤压相结合,它能够产生紧密的中期圆柱体。此外,所得模型定性地解释了在微操作实验中观察到的有丝分裂染色体异常的弹性特性,并深入了解了凝缩蛋白在与常见脆性位点相关的异常染色体结构形成中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4808/12068332/40158dab8a7f/KNCL_A_2497765_F0001_B.jpg

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