bims-micesi 2024-08-11 papers

Issue of 2024‒08‒11
four papers selected by
Valentina Piano, Uniklinik Köln

Nat Cell Biol. 2024 Aug 08.

Spindle architecture constrains karyotype evolution.

Jana Helsen, Md Hashim Reza, Ricardo Carvalho, Gavin Sherlock, Gautam Dey.

The eukaryotic cell division machinery must rapidly and reproducibly duplicate and partition the cell's chromosomes in a carefully coordinated process. However, chromosome numbers vary dramatically between genomes, even on short evolutionary timescales. We sought to understand how the mitotic machinery senses and responds to karyotypic changes by using a series of budding yeast strains in which the native chromosomes have been successively fused. Using a combination of cell biological profiling, genetic engineering and experimental evolution, we show that chromosome fusions are well tolerated up until a critical point. Cells with fewer than five centromeres lack the necessary number of kinetochore-microtubule attachments needed to counter outward forces in the metaphase spindle, triggering the spindle assembly checkpoint and prolonging metaphase. Our findings demonstrate that spindle architecture is a constraining factor for karyotype evolution.

DOI: https://doi.org/10.1038/s41556-024-01485-w

Curr Biol. 2024 Aug 05. pii: S0960-9822(24)00832-7. [Epub ahead of print]34(15): R741-R744

Mitosis: An expanded view of mitotic mechanisms that arose in evolution.

Ying Gu, Snezhana Oliferenko.

Mitosis exhibits astonishing evolutionary plasticity, with dividing eukaryotic cells differing in the organization of the mitotic spindle and the extent of nuclear envelope breakdown. A new study suggests that a multinucleated lifestyle may favor the evolution of closed nuclear division.

DOI: https://doi.org/10.1016/j.cub.2024.06.048

Bull Math Biol. 2024 Aug 03. 86(9): 113

Relaxation and Noise-Driven Oscillations in a Model of Mitotic Spindle Dynamics.

Dionn Hargreaves, Sarah Woolner, Oliver E Jensen.

During cell division, the mitotic spindle moves dynamically through the cell to position the chromosomes and determine the ultimate spatial position of the two daughter cells. These movements have been attributed to the action of cortical force generators which pull on the astral microtubules to position the spindle, as well as pushing events by these same microtubules against the cell cortex and plasma membrane. Attachment and detachment of cortical force generators working antagonistically against centring forces of microtubules have been modelled previously (Grill et al. in Phys Rev Lett 94:108104, 2005) via stochastic simulations and mean-field Fokker-Planck equations (describing random motion of force generators) to predict oscillations of a spindle pole in one spatial dimension. Using systematic asymptotic methods, we reduce the Fokker-Planck system to a set of ordinary differential equations (ODEs), consistent with a set proposed by Grill et al., which can provide accurate predictions of the conditions for the Fokker-Planck system to exhibit oscillations. In the limit of small restoring forces, we derive an algebraic prediction of the amplitude of spindle-pole oscillations and demonstrate the relaxation structure of nonlinear oscillations. We also show how noise-induced oscillations can arise in stochastic simulations for conditions in which the mean-field Fokker-Planck system predicts stability, but for which the period can be estimated directly by the ODE model and the amplitude by a related stochastic differential equation that incorporates random binding kinetics.

Keywords: Mitosis; Relaxation oscillation; Spindle; Stochastic simulation

DOI: https://doi.org/10.1007/s11538-024-01341-w

J Cell Biol. 2024 Nov 04. pii: e202308034. [Epub ahead of print]223(11):

Cyclin B3 is a dominant fast-acting cyclin that drives rapid early embryonic mitoses.

Pablo Lara-Gonzalez, Smriti Variyar, Shabnam Moghareh, Anh Cao Ngoc Nguyen, Amrutha Kizhedathu, Jacqueline Budrewicz, Aleesa Schlientz, Neha Varshney, Andrew Bellaart, Karen Oegema, Lee Bardwell, Arshad Desai.

Mitosis in early embryos often proceeds at a rapid pace, but how this pace is achieved is not understood. Here, we show that cyclin B3 is the dominant driver of rapid embryonic mitoses in the C. elegans embryo. Cyclins B1 and B2 support slow mitosis (NEBD to anaphase ∼600 s), but the presence of cyclin B3 dominantly drives the approximately threefold faster mitosis observed in wildtype. Multiple mitotic events are slowed down in cyclin B1 and B2-driven mitosis, and cyclin B3-associated Cdk1 H1 kinase activity is ∼25-fold more active than cyclin B1-associated Cdk1. Addition of cyclin B1 to fast cyclin B3-only mitosis introduces an ∼60-s delay between completion of chromosome alignment and anaphase onset; this delay, which is important for segregation fidelity, is dependent on inhibitory phosphorylation of the anaphase activator Cdc20. Thus, cyclin B3 dominance, coupled to a cyclin B1-dependent delay that acts via Cdc20 phosphorylation, sets the rapid pace and ensures mitotic fidelity in the early C. elegans embryo.

DOI: https://doi.org/10.1083/jcb.202308034