Wellcome Centre for Cell Biology

Near millimolar concentration of nucleosomes in mitotic chromosomes from late prometaphase into anaphase

Earnshaw Lab - Journal of Cell Biology

 

Images of cells for Earnshaw lab paper August 2024
How much does chromatin compact during mitosis? Using electron microscopy, we precisely measured the volume of chromosomes at different mitotic stages. We concluded that chromatin reaches a plateau between late prometaphase and early anaphase, with the concentration of nucleosomes approaching millimolar levels.

Authors

Cisneros-Soberanis, F., Simpson, E.L., Beckett, A.J., Pučeková, N., Corless, S., Kochanova, N.Y., Prior, I.A., Booth, D.G., and Earnshaw, W.C.

 

Summary of Paper by Natalia Kochanova, Earnshaw Lab

Chromosome compaction is essential during mitosis to ensure accurate segregation. However, a detailed quantitative analysis of chromosome geometry throughout mitosis has been lacking.

Cisneros-Soberanis and colleagues used serial block face scanning electron microscopy (SBF-SEM) to obtain nanometer-resolution reconstructions of full mitotic cells, from early prometaphase to telophase. During prometaphase, chromosomes acquire a smoother surface, their arms shorten, and the primary centromeric constriction forms. As mitosis progresses, chromatin progressively compacts, reaching an amazing nucleosome concentration of 750 µM during metaphase.

In anaphase, sister chromatids begin to separate, but the changes in chromosome width and length suggest that some catenation may persist, keeping them stretched. Chromosome volume increases in late anaphase just before the nuclear envelope reforms. This study also found that smaller chromosomes tend to move closer to the spindle poles compared to larger chromosomes.

The key finding of this research is that chromatin compaction reaches a plateau between late prometaphase and early anaphase, with nucleosome concentrations near millimolar levels. This apparent density limit is consistent with a process involving phase separation, although other mechanisms might explain it.

 

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