Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold

Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology
Mingxuan SunJohn F Marko

Abstract

During cell division, chromosomes must be folded into their compact mitotic form to ensure their segregation. This process is thought to be largely controlled by the action of condensin SMC protein complexes on chromatin fibers. However, how condensins organize metaphase chromosomes is not understood. We have combined micromanipulation of single human mitotic chromosomes, sub-nanonewton force measurement, siRNA interference of condensin subunit expression, and fluorescence microscopy, to analyze the role of condensin in large-scale chromosome organization. Condensin depletion leads to a dramatic (~ 10-fold) reduction in chromosome elastic stiffness relative to the native, non-depleted case. We also find that prolonged metaphase stalling of cells leads to overloading of chromosomes with condensin, with abnormally high chromosome stiffness. These results demonstrate that condensin is a main element controlling the stiffness of mitotic chromosomes. Isolated, slightly stretched chromosomes display a discontinuous condensing staining pattern, suggesting that condensins organize mitotic chromosomes by forming isolated compaction centers that do not form a continuous scaffold.

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Citations

Nov 24, 2019·Proceedings of the National Academy of Sciences of the United States of America·Sumitabha Brahmachari, John F Marko
Apr 22, 2020·Chromosoma·Kristina KleinschnitzStefan K Heidmann
Oct 3, 2020·Biochemical Society Transactions·Erin E Cutts, Alessandro Vannini
Dec 10, 2020·ELife·Edward J Banigan, Leonid A Mirny
Jul 3, 2020·Computational and Structural Biotechnology Journal·Tomáš BesedaHana Šimková
Dec 31, 2020·Cell & Bioscience·Hongzhen WangGuiying Li
Sep 21, 2019·Micron : the International Research and Review Journal for Microscopy·Rinyaporn PhengchatKiichi Fukui
Oct 15, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lingluo ChuNancy E Kleckner
Mar 27, 2021·Nature Reviews. Molecular Cell Biology·Iain F Davidson, Jan-Michael Peters
Aug 10, 2020·Molecular Cell·Andrews Akwasi AgblekeDushan Wadduwage
Apr 6, 2021·Frontiers in Cell and Developmental Biology·Margarida DantasJorge G Ferreira
Sep 18, 2021·Quarterly Reviews of Biophysics·T ManG J L Wuite
Aug 10, 2020·Molecular Cell·Lingluo ChuNancy Kleckner

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Methods Mentioned

BETA
Hi-C
transfection
fluorescence microscopy

Software Mentioned

Labview
Fiji
MetaMorph
ImageJ

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