๐ฐ "Meiotic cohesin paralogs govern cell survival by exhibiting flexibility in partner choice"
https://www.biorxiv.org/content/10.64898/2026.03.27.714714v1?rss=1 #Mitosis #Cell
Meiotic cohesin paralogs govern cell survival by exhibiting flexibility in partner choice
Erroneous loading of the ring-shaped cohesin complex, especially at centromeres, cause chromosomal segregation defects in both mitosis and meiosis. Mitotic cohesin subunits of this complex, either get replaced or co-exist with their meiotic paralogs during meiosis and also in certain cancers. However, it is unclear whether meiotic paralogs can partner mitotic subunits to form hybrid complexes in somatic cells and if there are any functional consequences on cancer progression. Here, we provide a conceptual framework for the principles of cohesin complex assembly involving non-canonical subunits in proliferating Schizosaccharomyces pombe. We show that chromosome loading, segregation fidelity and cellular proliferation are critically affected by the composition of the available cohesin complexes. We find stark differences in the ability of the meiotic kleisin subunit Rec8 to support robust centromere loading, irrespective of its partner, when compared to the canonical mitotic paralog Rad21. Such variations in cellular growth can be explained by different dwell times of these cohesin complexes on the chromosomes as determined by single-molecule tracking and altered chromatin enrichment. We also discover a unique feature of Rec8, in stabilizing chromatin-bound hypomorphic cohesin mutants that aid in cell survival under restrictive conditions. Overall, we highlight the flexibility of meiotic cohesins in restoring function, albeit at a fitness cost, in the presence of inactivating cohesin mutations. Such imbalances could be exploited by cancers to aid cell survival, but at the expense of increased aneuploidy and genomic instability.
### Competing Interest Statement
The authors have declared no competing interest.
Wellcome Trust/DBT India Alliance, https://ror.org/04reqzt68, IA/I/23/1/506752
Science and Engineering Research Board, https://ror.org/03ffdsr55, SPG/2022/000881
Department of Biotechnology, https://ror.org/03tjsyq23, BT/PR54475/BSA/33/357/2024(CN21105)
Expanding the C. elegans toolkit with gonad explants
Animal development is a complex process that requires the coordination of a plethora of pathways in space and time. In several species, the availability of tissue explants has provided a simplified context that facilitates mechanistic investigations, particularly into dynamic events. Here, we demonstrate that extruded C. elegans gonads are a viable tissue explant system for this model organism. Using live-cell imaging, we show that C. elegans gonad explants retain many tissue properties that have been documented in vivo, including mitosis, meiosis, apoptosis and gametogenesis. We further show that C. elegans explants are acutely responsive to treatment by the microtubule depolymerizing drug nocodazole. Our work thus reveals C. elegans gonad explants as a new system in which live-cell imaging and acute drug treatment can be combined to decipher the mechanisms governing germline development.
### Competing Interest Statement
The authors have declared no competing interest.
Canadian Institutes of Health Research, PJT-525829
๐ฐ "Centriolar satellites regulate CEP350 mRNA localization and centrosome amplification"
https://www.biorxiv.org/content/10.64898/2026.03.26.714479v1?rss=1 #Microtubule #Mitosis
Centriolar satellites regulate CEP350 mRNA localization and centrosome amplification
Messenger RNAs (mRNAs) accumulate at centrosomes in mitosis and interphase, yet the mechanisms governing their localization and the functional significance of centrosomal localization remain poorly understood. Here, we investigate the regulation and function of the centrosome-localized mRNA, CEP350. We find that CEP350 mRNA localizes to centrosomes during S phase via the centriolar satellite protein CEP131 and the RNA binding protein (RBP) Unkempt (UNK), in a microtubule (MT)-dependent manner. CEP131 and UNK stabilize CEP350 mRNA to maintain CEP350 mRNA steady-state levels. Furthermore, CEP131 and UNK promote normal CEP350 protein levels at centrosomes. CEP350 is required for PLK4-induced centriole overduplication but is less important for canonical centriole duplication. Moreover, CEP131, UNK, and CEP350 are important for centrosome amplification in triple-negative breast cancer cells. Together, these findings reveal a centriolar satellite-RBP pathway regulating CEP350 mRNA localization to centrosomes.
### Competing Interest Statement
The authors have declared no competing interest.
National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35 GM140813
W.M. Keck Science Center, https://ror.org/05sy8gb82, 211402
๐ฐ "RNAi-based discrimination of exogenous DNA by mitotic heterochromatin in fission yeast"
https://www.biorxiv.org/content/10.64898/2026.03.26.714489v1?rss=1 #Mitosis #Cell
RNAi-based discrimination of exogenous DNA by mitotic heterochromatin in fission yeast
Various mechanisms protect prokaryotic cells from invasive exogenous (exo)DNA. However, these are rarely conserved in eukaryotes, where the existence of such processes remains elusive. Here, we uncover how fission yeast eliminates exoDNA through unequal partitioning. We show that intrinsic transcriptional features of plasmidial exoDNA produce small interfering (si)RNAs that recruit heterochromatin onto the plasmid. An active, heterochromatin-dependent clustering mechanism then causes its asymmetric partitioning during mitosis. The mitotic kinase Aurora B, which dissociates heterochromatin on segregating chromosomes, is distinctively hypoactive on plasmidial DNA, facilitating its unequal partitioning and, ultimately, elimination from the cell population. Thus, an interplay between RNAi-mediated exoDNA heterochromatinization and chromosomal phosphorylation enables fission yeast to discriminate self- from non-self-DNA, uncovering a hitherto undescribed cell-autonomous immune process in eukaryotic cells.
### Competing Interest Statement
The authors have declared no competing interest.
ETH core funding
Advanced ECR grant (BarrAge)
ETH internal project grant, ETH-29 18-1
European Union's Horizon 2020 research and innovation programme grant, 899417, CIRCULAR VISION
German Research Foundation (DGF) through the Heisenberg Programme, 464293512
๐ฐ "CDK1-dependent N-terminal NuMA phosphorylation promotes dynein-dynactin-NuMA assembly for accurate chromosome segregation"
https://doi.org/doi:10.1016/j.celrep.2026.117170https://pubmed.ncbi.nlm.nih.gov/41880324/ #Microtubule #Mitosis
Microtubule end stabilisation by cooperative oligomers of Ska and Ndc80 complexes - The EMBO Journal
During mitosis, properly aligned chromosomes stabilise microtubule ends with the help of kinetochores to ensure timely segregation of chromosomes. Microtubule-binding components of the human outer kinetochore, such as Ndc80 and Ska complexes, are present in multiple copies and together bind several microtubule ends, creating a highly multivalent binding interface. Whereas Ndc80:Ndc80 and Ndc80:microtubule binding is crucial for interface stability, Ndc80 alone in absence of Ska is unable to support stable kinetochore-attachments. Using cryo-electron tomography, we demonstrate that oligomeric Ndc80:Ska assemblies stabilise microtubule ends against shortening by strengthening lateral contacts between tubulin protofilaments at microtubule plus-ends. We further identify a point mutation within the SKA1 microtubule-binding domain that does not affect microtubule-binding of individual Ska molecules, but does abolish Ska:Ska interactions. Finally, we report that oligomerisation of Ska, in a cooperative fashion together with the Ndc80, is necessary to maintain stable microtubule attachments both in vivo and in vitro.
๐ฐ "Development of MKI-3: A Potent and Selective MASTL Inhibitor with Improved Efficacy for Cancer Treatment"
https://doi.org/doi:10.1021/acs.jmedchem.5c03599https://pubmed.ncbi.nlm.nih.gov/41857504/ #Microtubule #Mitosis๐ฐ "lncRNA NORM is essential for proper chromosome segregation through the Plk1-Bub1 and Nsun2 axis."
https://www.biorxiv.org/content/10.64898/2026.03.15.711899v1?rss=1 #Mitosis #CelllncRNA NORM is essential for proper chromosome segregation through the Plk1-Bub1 and Nsun2 axis.
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