bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2025–10–05
eleven papers selected by
Valentina Piano, Uniklinik Köln
  1. Functional framework of the kinetochore and spindle assembly checkpoint in Arabidopsis.
  2. Plasmodium ARK1 regulates spindle formation during atypical mitosis and forms a divergent chromosomal passenger complex.
  3. The Chromatin Protein CFDP1 Activates TPX2 and Promotes Chromosomal Microtubule Nucleation and Spindle Assembly.
  4. Preserving centromere identity: right amounts of CENP-A at the right place and time.
  5. Reversible arginine methylation of PI3KC2α controls mitotic spindle dynamics.
  6. Mechanism of spindle stability and poleward flux regulating spindle length during the metaphase.
  7. Mitotic DNA repair by TMEJ suppresses replication stress-induced nuclear envelope reassembly defect.
  8. TUFT1 regulates cancer progression by suppressing centrosome amplification and mitotic spindle multipolarity.
  9. Flexibility or commitment: choosing between division and differentiation.
  10. Metal ion homeostasis regulates condensin-dependent chromatin architecture and chromosome segregation in Schizosaccharomyces pombe.
  11. Arabidopsis Dynamin-Related Protein 1a is important for cell plate fusion with parent cell plasma membrane in cytokinesis during pollen mitosis I.
  1. Plant Physiol. 2025 Sep 30. pii: kiaf461. [Epub ahead of print]
    Functional framework of the kinetochore and spindle assembly checkpoint in Arabidopsis.
    Aladár Pettkó-Szandtner, Zoltán Magyar, Shinichiro Komaki.
      The kinetochore, critical for accurate chromosome segregation and genome stability in eukaryotes, comprises the Constitutive Centromere Associated Network (CCAN) and the KMN network. In animals, the CCAN associates with centromeric nucleosomes throughout the cell cycle, while the KMN network assembles at kinetochores during M phase, binding spindle microtubules and serving as a platform for the spindle assembly checkpoint (SAC) complex. Despite conserved functions, kinetochore components vary across organisms. In this study, we investigated the subcellular localization and interaction maps of core kinetochore components in Arabidopsis (Arabidopsis thaliana). Of the four conserved CCAN components, we found that only Centromere protein C (CENP-C) localizes to kinetochores, while all KMN components consistently localize to the kinetochore throughout the cell cycle. Immunoprecipitation assays revealed interactions between core kinetochore proteins and regulators involved in DNA replication, histone modification, and chromatin remodeling, suggesting that the kinetochore may also function outside of M phase. Examining interactions between kinetochore and SAC components allowed us to elucidate plant-specific SAC localization mechanisms, providing a functional framework for understanding plant kinetochores and offering insights into SAC regulation in plants.
    DOI:  https://doi.org/10.1093/plphys/kiaf461
  2. Res Sq. 2025 Sep 25. pii: rs.3.rs-7473364. [Epub ahead of print]
    Plasmodium ARK1 regulates spindle formation during atypical mitosis and forms a divergent chromosomal passenger complex.
    Rita Tewari, Annu Nagar, Ryuji Yanase, Mohammad Zeeshan, David J P Ferguson, Steven Abel, Sarah Pashley, Akancha Mishra, Anthonius Eze, Edward Rea, Declan Brady, Andrew Bottrill, Sue Vaughan, Karine Le Roch, David Guttery, Anthony Holder, Eelco Tromer, Pushkar Sharma.
      Mitosis in Plasmodium spp., the causative agent of malaria, is fundamentally different from model eukaryotes, proceeding via a bipartite microtubule organising centre (MTOC) and lacking canonical regulators such as Polo and Bub1 kinases. During schizogony, asynchronous nuclear replication produces a multinucleate schizont, while rapid male gametogony generates an octaploid nucleus before gamete formation. Here, we identify Aurora-related kinase 1 (ARK1) as a key component of inner MTOC and spindle formation, controlling kinetochore dynamics and driving mitotic progression. Conditional ARK1 depletion disrupts spindle biogenesis, kinetochore segregation, karyokinesis and cytokinesis in both stages, and affects parasite transmission. Interactome analysis reveals ARK1 as the catalytic core of a non-canonical chromosomal passenger complex (CPC) containing two divergent inner centromere proteins (INCENPs) but lacking Survivin and Borealin. Comparative genomics indicates this CPC architecture arose early in Apicomplexa, replacing canonical centromere-targeting modules. These findings uncover a distinct mitotic machinery in Plasmodium and identify the ARK1-INCENP interface as a potential multistage target for malaria therapeutic intervention.
    DOI:  https://doi.org/10.21203/rs.3.rs-7473364/v1
  3. bioRxiv. 2025 Sep 22. pii: 2025.09.22.677689. [Epub ahead of print]
    The Chromatin Protein CFDP1 Activates TPX2 and Promotes Chromosomal Microtubule Nucleation and Spindle Assembly.
    Gokul Gopinathan, Xianghong Luan, Thomas G H Diekwisch.
      Microtubule associated proteins (MAPs) are multifunctional tubulin-binding proteins that contribute to essential aspects of mitotic spindle formation. In the present study, loss of the MAP CFDP1 in mice resulted in gastrulation defects and embryonic lethality at e8.5 due to chromosome segregation spindle defects and loss of K-fiber stability. CFDP1 decreased the association of the nuclear transport protein importin α with the essential spindle assembly factor TPX2, thereby promoting Aurora A kinase activation, microtubule nucleation and spindle assembly. Further defining CFDP1 mode of action we identified CFDP1 as a bipartite molecule with an acidic N-terminus that harbors a nuclear localization signal essential for importin α dissociation from TPX2 and a basic C-terminus that interacts with tubulin, co-localizes with the mitotic spindle, and promotes microtubule bundling and polymerization. Together, our studies have established CFDP1 as an essential bipartite MAP involved in chromosomal microtubule nucleation in conjunction with TPX2 and Aurora A while also facilitating nuclear TPX2 activation through importin α dissociation.
    DOI:  https://doi.org/10.1101/2025.09.22.677689
  4. Chromosome Res. 2025 Sep 30. 33(1): 21
    Preserving centromere identity: right amounts of CENP-A at the right place and time.
    Zofia Pukało, Bethan Medina-Pritchard, Maria Alba Abad, A Arockia Jeyaprakash.
      Four decades ago, the discovery of centromere protein-A (CENP-A) marked a pivotal breakthrough in chromosome biology, revealing the epigenetic foundation of centromere identity. CENP-A, a histone H3 variant, directs the formation of the microtubule-binding kinetochore complex, designating the chromosomal site for its assembly and underpins the accurate partitioning of genetic material during cell division. Errors in cell division can give rise to DNA instability and aneuploidy, implicated in human diseases such as cancer. Therefore, discovering the underlying pathways and mechanisms responsible for the formation, regulation and maintenance of the centromere is important to our understanding of genome stability, epigenetic inheritance, and in providing the knowledge to help generate possible treatments and therapeutics. Here, we review various molecular pathways and mechanisms implicated in maintaining centromere identity and highlight some of the key outstanding questions with a focus on the human centromere.
    Keywords:  CENP-A; Centromere; Mis18; Regulation; Transcription; Ubiquitination
    DOI:  https://doi.org/10.1007/s10577-025-09780-4
  5. Cell Commun Signal. 2025 Oct 02. 23(1): 409
    Reversible arginine methylation of PI3KC2α controls mitotic spindle dynamics.
    Yena Cho, Jee Won Hwang, Mark T Bedford, Dong Hee Na, Dae-Geun Song, Su-Nam Kim, Yong Kee Kim.
      Microtubules, composed of αβ-tubulin dimers, undergo dynamic polymerization and are fundamental to cell structure and function. In the current study, we discovered that phosphatidylinositol 3-kinase class 2α (PI3KC2α) acts as a novel regulatory factor in microtubule dynamics. Specifically, asymmetric dimethylation of PI3KC2α at the R175 residue (R175me2a) by coactivator-associated arginine methyltransferase 1 (CARM1) enhances its interaction with α-tubulin, stabilizing microtubule assembly. Furthermore, lysine Demethylase 4 A (KDM4A) serves as an arginine demethylase for PI3KC2α R175me2a. During mitosis, protein kinase C (PKC)-mediated phosphorylation of KDM4A results in its dissociation from PI3KC2α, preventing demethylation and increasing R175me2a levels. This facilitates spindle formation and highlights the critical role of reversible arginine methylation in regulating mitotic spindle dynamics. Cumulatively, these findings reveal the coordinated interplay between CARM1 and KDM4A in modulating microtubule behavior through PI3KC2α R175 methylation, offering new insights into the regulatory mechanisms of mitotic progression.
    Keywords:  Autoregulation; CARM1; Microtubule; Mitosis; PI3KC2α; Tubulin
    DOI:  https://doi.org/10.1186/s12964-025-02419-1
  6. iScience. 2025 Oct 17. 28(10): 113506
    Mechanism of spindle stability and poleward flux regulating spindle length during the metaphase.
    Yao Wang, Yu-Ru Liu, Peng-Ye Wang, Hui Li, Ping Xie.
      During metaphase, the spindle stabilizes chromosomes and maintains its size despite continuous microtubule poleward flux. To investigate the mechanism of the spindle stability and how the poleward flux regulates the spindle size, we establish a minimal spindle model that incorporates kinetochores, microtubules, spindle poles, and microtubule sliding proteins such as kinesin-5, microtubule depolymerizing proteins such as kinesin-13, and microtubule crosslinking proteins such as NuMA. We find that the poleward flux stabilizes the spindle by regulating the spindle length and the length of antiparallel microtubule overlaps to achieve equal rates of microtubule sliding, plus-end polymerization, and minus-end depolymerization. We reveal the underlying mechanism of how the poleward flux rate scales linearly with the spindle length and microtubule overlap length in small cells and how microtubule nucleation affects spindle dynamics in large cells.
    Keywords:  Bioinformatics; Cell biology; Organizational aspects of cell biology
    DOI:  https://doi.org/10.1016/j.isci.2025.113506
  7. Nat Commun. 2025 Oct 03. 16(1): 8836
    Mitotic DNA repair by TMEJ suppresses replication stress-induced nuclear envelope reassembly defect.
    Guojun Ye, Yide He, Yihui Zhang, Dongchen Li, Fuhai Liu, Yi Li, Qinglian Ge, Qiong Guo, Shuya Han, Chunyu Song, Weiping Chang, Haoyue Zhang, Qin Peng, Kun Sun, Weike Ji, Lin Deng.
      Replication stress (RS), if not effectively and timely addressed, could result in DNA damage in mitosis. However, the relationship between RS and other mitotic events, such as nuclear envelope (NE) breakdown and reassembly, remains poorly understood. Here we report that RS can lead to NE defect. Importantly, rather than de novo NE rupture, the defect per se is a result of nuclear envelope reassembly defect (NERD) during mitosis. Interestingly, NERD is associated with mitotic DNA damage, and repair of the damage by DNA polymerase theta (Polθ)-mediated end joining (TMEJ) ameliorates NERD. Genomic mapping of lamina associated domains (LADs) by cleavage under targets and tagmentation (CUT&Tag) identifies a population of replication stress-sensitive LADs (RESSLADs). Strikingly, a substantial portion of RESSLADs reside in the common fragile sites (CFSs). The loss of RESSLADs-NE interaction under RS might be attributed to the sustained phosphorylation of Lamin A/C at the sites of NERD. In addition, prominent NE defect is observed under multiple conditions of synthetic lethality. Altogether, these findings establish a link between genome instability and nuclear vulnerability under replication stress.
    DOI:  https://doi.org/10.1038/s41467-025-63942-w
  8. Cell Death Dis. 2025 Sep 29. 16(1): 673
    TUFT1 regulates cancer progression by suppressing centrosome amplification and mitotic spindle multipolarity.
    Shaojie Feng, Mengmeng Zhao, Donghui Zhang, Yan Zhang, Lingyuan Min, Xianqiang Liu, Huan Shi, Tianning Wang.
      Centrosome amplification (CA) has been observed in various solid tumors and contributes to chromosomal instability (CIN) and poor clinical prognosis in patients with cancer. CA also inhibits cell proliferation by inducing cell-cycle arrest and cell death. However, the mechanism of regulation of centrosome number in cancer cells and its effect on CIN and cell proliferation remains elusive. Here, we report that tuftelin (TUFT1) is a novel centrosomal protein that localizes to the proximal ends of parent centrioles. TUFT1 prevents CA and mitotic spindle multipolarity by suppressing premature polo-like kinase 1 activation. In addition, TUFT1 is phosphorylated by NIMA-related kinase 2 (NEK2), and the phosphorylation status of TUFT1 is essential for coordinating centrosome number and cell proliferation in cervical and breast cancers. Data from clinical breast cancer samples indicate that the combined detection of TUFT1 and NEK2 expression reflects tumor malignancy and patient survival with higher precision. Overall, these results reveal a crucial role of TUFT1 in the regulation of tumor progression through centrosome number control. Thus, TUFT1 represents a promising target for diagnostic and therapeutic approaches for cancers.
    DOI:  https://doi.org/10.1038/s41419-025-08010-3
  9. J Exp Bot. 2025 Sep 30. pii: eraf429. [Epub ahead of print]
    Flexibility or commitment: choosing between division and differentiation.
    Pablo González-Suárez, Margot E Smit.
      As cells move from acquiring a specific identity to gaining cell type-specific functions during differentiation, their properties and programs need to be adjusted. Initially, most newly specified cells show high division potential and properties that confer them qualities reminiscent of stem cells. During maturation, however, cells exit or change division programs and gain differentiation characteristics. Factors that regulate this progression have often been described to control either division or differentiation but are now more often being linked to both sides of this trade-off. In this review, we provide an overview of recent publications that identify some of the factors balancing division and differentiation. We discuss these in the context of the tissues and cell types they act in and note connections to cell cycle regulation. Recent advances are now allowing for a better understanding of how division and differentiation programs intertwine to shape cell trajectories.
    Keywords:  Arabidopsis; cell death; cell fate; development; differentiation; division; endoreduplication; mitosis; quiescence; stem cell
    DOI:  https://doi.org/10.1093/jxb/eraf429
  10. J Microbiol. 2025 Sep;63(9): e2505008
    Metal ion homeostasis regulates condensin-dependent chromatin architecture and chromosome segregation in Schizosaccharomyces pombe.
    Seong Ho An, Kyoung-Dong Kim.
      Condensin plays a central role in mitotic chromosome organization and segregation by mediating long-range chromatin interactions. However, the extent to which cellular metabolic status influences condensin function remains unclear. To gain insights into the relationship of metal ion homeostasis and the function of condensin, we conducted genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) using Schizosaccharomyces pombe under iron- or zine-deficient conditions. Under iron- or zinc-deficient conditions, ChIP-seq results revealed a selective reduction in condensin binding at high-affinity target loci, particularly genes regulated by Ace2 and Ams2, while cohesin binding remained largely unaffected. Hi-C analysis showed that iron depletion weakened chromatin interactions at these condensin targets and centromeres, without disrupting global genome architecture. DNA fluorescence in situ hybridization (FISH) confirmed that iron deficiency impaired long-range associations between centromeres and Ace2 target loci at the single-cell level. Notably, iron deficiency led to chromosome segregation defects during mitosis, suggesting that diminished condensin occupancy compromised genome stability. These changes occurred without significant alterations in condensin protein levels or global transcription, indicating a direct effect of metal ion availability on condensin activity. Collectively, our findings revealed a previously unrecognized regulatory axis in which cellular metal ion homeostasis modulated condensin-dependent chromatin organization and mitotic chromosome segregation, offering new insights into the integration of metabolic state with genome maintenance.
    Keywords:  Schizosaccharomyces pombe; condensin; genome organization; metal ion homeostasis
    DOI:  https://doi.org/10.71150/jm.2505008
  11. Planta. 2025 Sep 29. 262(5): 110
    Arabidopsis Dynamin-Related Protein 1a is important for cell plate fusion with parent cell plasma membrane in cytokinesis during pollen mitosis I.
    Nan Wang, Qingchen Rui, Haoyue Xu, Xiaoyun Tan.
       MAIN CONCLUSION: Arabidopsis Dynamin-Related Protein 1a is important for mediating cell plate-parental membrane fusion during pollen mitosis I by regulating the formation of finger-like projections at the margin of the cell plate. Pollen mitosis I (PMI) is critical for pollen development, and the fusion of the cell plate with the parental plasma membrane is one of the most essential events during cytokinesis in PMI. However, the molecular mechanisms underlying this process remain largely unknown. In this study, we show that Arabidopsis Dynamin-Related Protein 1a (DRP1a), a multidomain GTPase regulating membrane remodeling processes such as fission, fusion, and tubulation, is required for cell plate fusion with the parental plasma membrane during PMI. Loss of DRP1a function leads to pollen abortion, with most drp1a mutant pollen grains failing to complete cell plate-parental membrane fusion. Further analysis revealed that in wild-type microspores, finger-like projections extend from the margins of the expanding cell plate and establish contact at the plasma membrane's adhesion zone. However, these structures were absent in cytokinesis-defective pollen grains from drp1a/ + mutants. Notably, DRP1a-YFP localized specifically to the cell plate margins, suggesting its direct involvement in this process. Our findings demonstrate that DRP1a, a member of the Dynamin-Related Protein family known for its roles in membrane remodeling, is important for mediating cell plate-parental membrane fusion during PMI by regulating the formation of finger-like projections.
    Keywords:  Cell plate fusion; Cytokinesis; Dynamin-Related Protein; Pollen mitosis I (PMI)
    DOI:  https://doi.org/10.1007/s00425-025-04832-9
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