bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2025–10–26
nine papers selected by
Valentina Piano, Uniklinik Köln
  1. Kinetochore-centrosome feedback linking CENP-E and Aurora kinases controls chromosome congression.
  2. Polo kinase inhibits protein phosphatase 1 to promote the spindle assembly checkpoint and prevent aneuploidy.
  3. Mechanical coordination between anaphase A and B drives asymmetric chromosome segregation.
  4. CENP-E initiates chromosome congression by opposing Aurora kinases to promote end-on attachments.
  5. Revisiting the question: When is a centromere not a kinetochore?
  6. Live imaging of late-stage preimplantation human embryos reveals de novo mitotic errors.
  7. Peculiarities of the mammalian oocyte cell cycle.
  8. Catalogue of mitotic chromosome-associated small RNAs in mouse 3T3 cell line.
  9. APC/C coactivators Cdh1 and Cdc20: Mechanistic insights into cancer progression and therapeutic opportunities.
  1. Nat Commun. 2025 Oct 21. 16(1): 9097
    Kinetochore-centrosome feedback linking CENP-E and Aurora kinases controls chromosome congression.
    Kruno Vukušić, Iva M Tolić.
      Chromosome congression is crucial for accurate cell division, with key roles played by kinetochore components, the molecular motor CENP-E/kinesin-7, and Aurora B kinase. However, Aurora B kinase can both inhibit and promote congression, suggesting the presence of a larger signaling network. Our study demonstrates that centrosomes inhibit congression initiation when CENP-E is inactive by regulating the activity of kinetochore components. Depletion of centrioles via Plk4 kinase inhibition allows chromosomes near acentriolar poles to initiate congression independently of CENP-E. At centriolar poles, high Aurora A kinase enhances Aurora B activity, increasing phosphorylation of microtubule-binding proteins at kinetochores and preventing stable microtubule attachments in the absence of CENP-E. Conversely, inhibition of Aurora A or expression of a dephosphorylatable mutant of the kinetochore microtubule-binding protein Hec1 enables congression initiation without CENP-E. We propose a negative feedback mechanism involving Aurora kinases and CENP-E that regulates the timing of chromosome movement by modulating kinetochore-microtubule attachments and fibrous corona expansion, with the Aurora A activity gradient providing critical spatial cues for the network's function.
    DOI:  https://doi.org/10.1038/s41467-025-64804-1
  2. Curr Biol. 2025 Oct 22. pii: S0960-9822(25)01249-7. [Epub ahead of print]
    Polo kinase inhibits protein phosphatase 1 to promote the spindle assembly checkpoint and prevent aneuploidy.
    Margarida Moura, João Barbosa, Inês Pinto, Nelson Leça, Sofia Cunha-Silva, Arianna Esposito Verza, Paulo D Pedroso, Sarah Lemaire, Joana Duro, Miguel Simoes-da-Silva, André Oliveira, Ricardo Reis, Jakob Nilsson, Claudio Sunkel, Andrea Musacchio, Mathieu Bollen, Carlos Conde.
      Protein phosphatase 1 (PP1) is essential for spindle assembly checkpoint (SAC) silencing and mitotic exit, but its regulation during mitosis remains ill-defined. Here, we demonstrate in vitro and in Drosophila cells that the mitotic kinase Polo phosphorylates PP1α87B at a conserved residue (T286) within a pocket implicated in the recognition of RVxF-containing target proteins. Phosphorylation of T286 inhibits PP1α87B binding to the RVxF motif of the SAC kinase MPS1, dampening the dephosphorylation of the MPS1 T-loop. Phosphorylation of T286 is dynamically regulated during mitosis. It occurs at unattached/tensionless kinetochores and decreases as chromosomes congress. Expression of phosphomimetic PP1α87BT286D prevents MPS1 inactivation in metaphase and causes a SAC-dependent delay of anaphase onset. Conversely, an unphosphorylatable PP1α87BT286A mutant impairs MPS1 activation at unattached kinetochores and weakens the SAC. In vivo, larval neuroblasts expressing PP1α87BT286 phosphomutants exhibit chromosome mis-segregation and aneuploidy. Thus, our findings identify Polo-mediated phosphorylation of PP1α87B as a critical regulatory strategy that fine-tunes phosphatase activity to ensure a robust and timely SAC and prevent genome instability.
    Keywords:  MPS1; PP1; Polo/PLK1; kinetochore; mitosis; spindle assembly checkpoint
    DOI:  https://doi.org/10.1016/j.cub.2025.09.049
  3. J Cell Biol. 2026 Jan 05. pii: e202505038. [Epub ahead of print]225(1):
    Mechanical coordination between anaphase A and B drives asymmetric chromosome segregation.
    Ana M Dias Maia Henriques, Timothy R Davies, Serge Dmitrieff, Nicolas Minc, Julie C Canman, Julien Dumont, Gilliane Maton.
      Chromosome segregation during anaphase occurs through two mechanistically distinct processes: anaphase A, in which chromosomes move toward spindle poles, and anaphase B, in which the anaphase spindle elongates through cortical astral microtubule pulling forces. Caenorhabditis elegans embryos have been thought to rely primarily on anaphase B, with little to no contribution from anaphase A. Here, we uncover a novel anaphase A mechanism in C. elegans embryos, driven by the kinesin-13 KLP-7MCAK and opposed by the kinesin-12 KLP-18. We found that the extent of chromosome segregation during anaphase A is asymmetrically regulated by cell polarity cues and modulated by mechanical tension within the spindle, generated by opposing forces acting on chromosomes and spindle poles. Additionally, we found that the contribution of anaphase A to chromosome segregation increases progressively across early embryonic divisions. These findings uncover an unexpected role for anaphase A in early C. elegans development and reveal a KLP-7MCAK-dependent mechanical coordination between anaphase A- and anaphase B-driven chromosome segregation.
    DOI:  https://doi.org/10.1083/jcb.202505038
  4. Nat Commun. 2025 Oct 21. 16(1): 8537
    CENP-E initiates chromosome congression by opposing Aurora kinases to promote end-on attachments.
    Kruno Vukušić, Iva M Tolić.
      Accurate cell division relies on rapid chromosome congression. The kinetochore motor protein CENP-E/kinesin-7 is uniquely required for congression of polar chromosomes. It is currently assumed that CENP-E drives congression by gliding kinetochores along microtubules independently of their biorientation. Here, by studying chromosome movement under different levels of CENP-E activity, we favor an alternative model in which CENP-E initiates congression by promoting stabilization of end-on attachments. In this way, CENP-E accelerates congression initiation without significantly contributing to subsequent movement. Stabilization of end-on attachments on polar chromosomes without CENP-E is delayed due to Aurora kinase-mediated hyperphosphorylation of microtubule-binding proteins and expansion of the fibrous corona. CENP-E counters this by reducing Aurora B-mediated phosphorylation in a BubR1-dependent manner, thereby stabilizing initial end-on attachments, facilitating removal of the fibrous corona, and triggering biorientation-dependent chromosome movement. These findings support a unified model of chromosome movement in which congression is intrinsically coupled to biorientation.
    DOI:  https://doi.org/10.1038/s41467-025-64148-w
  5. Chromosome Res. 2025 Oct 25. 33(1): 23
    Revisiting the question: When is a centromere not a kinetochore?
    Samuel Corless, Gokilavani Thangavel, Sylvia Erhardt.
      Centromeres have been the focus of extensive research for almost a century, so it may come as a surprise that a consistent definition and nomenclature for these structures remains elusive. In recent times, centromeric chromatin is most frequently defined by the presence of nucleosomes containing the H3 variant CENP-A and is typically synonymous with the site of the inner-kinetochore. However, crucial mammalian centromere proteins including CENP-B and INCENP have well defined distributions that show very little overlap with CENP-A. Additional protein localisations spanning the primary constriction or forming a band below CENP-A chromatin have been reported. Together, these observations suggest a complex and multi-layered chromatin organisation that is not well served by the canonical dichotomy of 'centromeric' and 'pericentromeric' chromatin. Strikingly, this is not a new observation but was made soon after the discovery of CENP proteins, including in a 1991 publication titled 'When is the centromere not a kinetochore?'. Here we revisit this question, which has become more pertinent following technical innovations in long-read sequencing and super-resolution microscopy. We present a model of centromere organisation for monocentromeres that incorporates additional complexity. We then use this model to reconceptualise diverse centromere forms in other eukaryotes including regional centromeres, holocentromeres and centromeres that lack key proteins including CENP-A. In this way, we hope to move towards a unified understanding of centromeric chromatin.
    Keywords:  Centromere; Chromatin organisation; Kinetochore; Satellite DNA
    DOI:  https://doi.org/10.1007/s10577-025-09782-2
  6. Nat Biotechnol. 2025 Oct 23.
    Live imaging of late-stage preimplantation human embryos reveals de novo mitotic errors.
    Ahmed Abdelbaki, Afshan McCarthy, Anita Karsa, Leila Muresan, Kay Elder, Athanasios Papathanasiou, Phil Snell, Leila Christie, Martin Wilding, Benjamin J Steventon, Kathy K Niakan.
      Existing methods to image chromosome segregation errors are not suitable for studying human embryos at advanced preimplantation stages. As chromosomal errors are a leading cause of miscarriage and infertility, it remains unclear whether missegregation arises postfertilization. Here we optimize nuclear DNA labeling via messenger RNA electroporation and apply light-sheet live imaging to reveal chromosome segregation errors immediately before implantation. We show that embryos at advanced preimplantation stages display missegregation, including multipolar spindle formation, lagging chromosomes, misalignment and mitotic slippage. Most lagging chromosomes are passively inherited rather than reincorporated. To trace individual nuclei, we developed an open-source, semi-automated segmentation method using a customized deep learning model optimized for variability in embryo size, shape and signal. With this approach, we find most labeled cells remain externally positioned, consistent with placental rather than inner cell mass fate. Our findings raise questions about clinical uses of preimplantation genetic testing for aneuploidy, while providing broadly applicable imaging and segmentation methods for studying diverse cellular structures in human embryos.
    DOI:  https://doi.org/10.1038/s41587-025-02851-1
  7. Physiology (Bethesda). 2025 Oct 21.
    Peculiarities of the mammalian oocyte cell cycle.
    Benjamin Wetherall, Suzanne Madgwick.
      Oocyte meiosis, the process of egg cell formation, requires a highly regulated cell cycle with many unique features compared to somatic cell division. On the journey to create a healthy embryo, this special cell carries a heavy responsibility and must navigate a remarkable number of complex challenges. Most oocytes will never complete this journey, less than 0.1% are ever ovulated, and fewer are viable. However, the few that do complete, manage by the execution of a series of extraordinary adaptations through two rounds of cell division. In this review we discuss some of these challenges and the adaptations that have evolved to mitigate them. This is not intended to be a comprehensive review of the cell cycle in oocytes meiosis, but to highlight some of the differences between oocyte meiosis and a typical mitosis. We discuss features that make this cell unique and the cell cycle regulatory mechanisms that support them. A salute to the few that make it and those that are sacrificed along the way.
    Keywords:  Aneuploidy; Cell cycle; Fertility; Meiosis; Oocyte
    DOI:  https://doi.org/10.1152/physiol.00027.2025
  8. Front Genet. 2025 ;16 1559795
    Catalogue of mitotic chromosome-associated small RNAs in mouse 3T3 cell line.
    Bishan Ye, Yicong Meng, Le Zhang, Yongzhuo Deng, Xuesong Zheng, Yihang Shen, Xinhui Li, Hua Li.
      
    Keywords:  RNA sequencing; microRNA; mitotic chromosomes; mouse 3T3 cells; small RNAs
    DOI:  https://doi.org/10.3389/fgene.2025.1559795
  9. Cell Signal. 2025 Oct 21. pii: S0898-6568(25)00586-8. [Epub ahead of print] 112171
    APC/C coactivators Cdh1 and Cdc20: Mechanistic insights into cancer progression and therapeutic opportunities.
    Yaqi Zhang, Haoyi Wang, Kaifan Li, Xu Xu, Qingya Yan, Yunqin Sun, Yaofeng Wang, Huitong Bu, Xinyi Liang, Qian Hao, Bo Gao, Xiang Zhou, Tao Han, Liping Guan.
      The dysregulation of the cell cycle is intricately linked to the pathogenesis and progression of numerous human diseases, especially for malignant tumors. The anaphase-promoting complex/cyclosome (APC/C), an evolutionarily conserved protein complex, plays a pivotal role in regulating the metaphase-to-anaphase transition during mitosis, making it indispensable for cellular division. APC/C requires binding to co-activators Cdh1 (also known as Fizzy-related protein 1, Cdh1) and Cdc20 (cell division cycle 20 homolog, also called Fizzy) to form the enzymatically active APC/CCdh1 and APC/CCdc20 complexes.This review provides a comprehensive synthesis of recent advancements in deciphering the multifaceted roles of APC/C coactivators Cdh1 and Cdc20 in cancer initiation, progression, and therapeutic. We first outline the structural architecture and functional mechanisms of APC/C, then dissect the distinct patterns of dysregulation exhibited by Cdh1 and Cdc20 in human malignancies. Additionally, we discuss current developments in APC/C-targeting inhibitors, explore innovative therapeutic strategies leveraging APC/C modulation, and identify emerging frontiers for future research.
    Keywords:  APC/C; Cdc20; Cdh1; Inhibitors; Tumorigenesis; Ubiquitination
    DOI:  https://doi.org/10.1016/j.cellsig.2025.112171
This page is being maintained by Thomas Krichel. It was last updated on 2025‒11‒10 at 9:02.