bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2025–06–15
twenty papers selected by
Valentina Piano, Uniklinik Köln
  1. Hypothesis that ancestral eukaryotes sexually proliferated without kinetochores or mitosis.
  2. CTCF maintains pericentromere function and mitotic fidelity.
  3. A distinct phase of cyclin B (Cdc13) nuclear export at mitotic entry in S. pombe.
  4. The fine art of chromatin folding: Revealing the path of DNA inside mitotic chromosomes.
  5. KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis.
  6. Orderly mitosis shapes interphase genome architecture.
  7. The stn1-sz2 Mutant Provides New Insight into the Impacts of Telomeric Cdc13-Stn1-Ten1 Dysfunction on Cell Cycle Progression.
  8. Mitotic genome folding.
  9. Identification of chromatin-associated RNAs at human centromeres.
  10. Mitotic chromosomes harbor cell type and species-specific structural features within a universal loop array conformation.
  11. Replication stress alters CENP-A nucleosome stability during S phase.
  12. Mechanical force locally damages, remodels and stabilizes the lattice of spindle microtubules.
  13. An Auxin Inducible Degradation System to Study Mklp2 Functions in MDCK Epithelial Cells.
  14. Making Two out of One: Kinesin Motors Driving Plant Cell Division.
  15. Mechanosensitive nuclear checkpoint: nuclear envelope as a sensor of chromosomal instability and driver of cell fate.
  16. Differential sensitivity of midline development to mitosis during and after primitive streak extension.
  17. CLASP1 regulates Dynein for PLK1-mediated spindle organization and cytokinesis in oocyte meiosis.
  18. Solution conformational differences between conventional and CENP-A nucleosomes are accentuated by reversible deformation under high pressure.
  19. AURKA inhibition amplifies DNA replication stress to foster WEE1 kinase dependency and synergistic antitumor effects with WEE1 inhibition in cancers.
  20. Cilia at the crossroad: convergence of regulatory mechanisms to govern cilia dynamics during cell signaling and the cell cycle.
  1. J Cell Sci. 2025 Jun 01. pii: jcs263843. [Epub ahead of print]138(11):
    Hypothesis that ancestral eukaryotes sexually proliferated without kinetochores or mitosis.
    Bungo Akiyoshi.
      Eukaryotes possess two different mechanisms to transmit genetic material - mitosis and meiosis. Because mitosis is universal in all present-day eukaryotes, it has been widely assumed, despite the absence of definitive evidence, that meiosis evolved from mitosis during eukaryogenesis. In both processes, chromosome movement depends on interactions between spindle microtubules and a macromolecular protein complex called the kinetochore that assembles onto centromere DNA. Spindle microtubules consist of α- and β-tubulin subunits, which are conserved in all studied eukaryotes. Similarly, canonical kinetochore components are found in almost all eukaryotes. However, an evolutionarily divergent group of organisms called kinetoplastids has a unique set of kinetochore proteins. It remains unclear why and when different types of kinetochores evolved. In this Hypothesis article, I propose that the last eukaryotic common ancestor (LECA) did not have a kinetochore and that these two kinetochore systems evolved independently - one in the ancestor of kinetoplastids and another in the ancestor of all other eukaryotes. Based on the notion that archaea and the LECA possessed cell fusion and genetic exchange machineries, I further propose that key aspects of meiosis evolved prior to mitosis, challenging the dogma that meiosis evolved from mitosis.
    Keywords:  Cell fusion; Eukaryogenesis; Eukaryote; Genetic exchange; Kinetochore; Meiosis; Mitosis; Prokaryote
    DOI:  https://doi.org/10.1242/jcs.263843
  2. bioRxiv. 2025 Jun 03. pii: 2025.05.30.657091. [Epub ahead of print]
    CTCF maintains pericentromere function and mitotic fidelity.
    Erin Walsh, Andrew D Stephens.
      In mitosis the duplicated genome is aligned and accurately segregated between daughter nuclei. CTCF is a chromatin looping protein in interphase with an unknown role in mitosis. We previously published data showing that CTCF constitutive knockdown causes mitotic failure, but the mechanism remains unknown. To determine the role of CTCF in mitosis, we used a CRISPR CTCF auxin inducible degron cell line for rapid degradation. CTCF degradation for 3 days resulted in increased failure of mitosis and decreased circularity in post-mitotic nuclei. Upon CTCF degradation CENP-E is still recruited to the kinetochore and there is a low incidence of polar chromosomes which occur upon CENP-E inhibition. Instead, immunofluorescence imaging of mitotic spindles reveals that CTCF degradation causes increased intercentromere distances and a wider and more disorganized metaphase plate, a disruption of key functions of the pericentromere. These results are similar to partial loss of cohesin, an established component of the pericentromere. Thus, we reveal that CTCF is a key maintenance factor of pericentromere function, successful mitosis, and post-mitotic nuclear shape.
    DOI:  https://doi.org/10.1101/2025.05.30.657091
  3. bioRxiv. 2025 Jun 06. pii: 2025.06.05.658100. [Epub ahead of print]
    A distinct phase of cyclin B (Cdc13) nuclear export at mitotic entry in S. pombe.
    Samir G Chethan, Jessie M Rogers, Drisya Vijayakumari, Wendi Williams, Vojislav Gligorovski, Sahand Jamal Rahi, Silke Hauf.
      In eukaryotes, cell division requires coordination between the nucleus and cytoplasm. Entry into cell division is driven by cyclin-dependent kinases (CDKs), which need a cyclin binding partner for their activity. In Schizosaccharomyces pombe (fission yeast), the B-type cyclin Cdc13 is essential and sufficient for cell cycle progression and is strongly enriched in the nucleus. Here, we show that a fraction of Cdc13 is exported from the nucleus to the cytoplasm just prior to mitosis. This export could be critical to propagate CDK activity throughout the cell. Mutating three Cdc13 nuclear localization signals (NLSs) led to precocious enrichment of Cdc13 in the cytoplasm but did not accelerate mitotic entry, indicating that the export is not sufficient to trigger entry into mitosis. The export coincides with spindle pole body integration into the nuclear envelope and may be required to coordinate nuclear and cytoplasmic signaling required for this integration. The onset and stop of Cdc13 nuclear export are remarkably abrupt, underscoring that S. pombe mitotic entry consists of several switch-like transitions over the course of minutes. Our findings add another instance to the various cyclin nuclear transport events known to occur at critical cell cycle transitions throughout eukaryotes.
    DOI:  https://doi.org/10.1101/2025.06.05.658100
  4. Cell Genom. 2025 Jun 11. pii: S2666-979X(25)00177-6. [Epub ahead of print]5(6): 100921
    The fine art of chromatin folding: Revealing the path of DNA inside mitotic chromosomes.
    Marina Vitoria Gomes, Christian H Haering.
      How chromatin fibers fold into rod-shaped mitotic chromosomes has long been a central question in genome biology. Two new studies now reconstruct the path of DNA in human chromosomes at nanoscale resolution and reveal how loop-extruding molecular machines fold chromatin into compact, rod-shaped structures at the onset of mitosis. Using microscopy- or sequencing-based approaches, respectively, both studies converge on similar models of chromosome organization yet differ in key mechanistic details. The findings further challenge textbook hypotheses of higher-order chromatin structures and reignite the quest for a detailed understanding of genome architecture inside living cells.
    DOI:  https://doi.org/10.1016/j.xgen.2025.100921
  5. Nucleic Acids Res. 2025 Jun 06. pii: gkaf476. [Epub ahead of print]53(11):
    KIF2C condensation concentrates PLK1 and phosphorylated BRCA2 on kinetochore microtubules in mitosis.
    Anastasiia Skobelkina, Manon Julien, Sylvain Jeannin, Simona Miron, Tom Egger, Rady Chaaban, Guillaume Bouvignies, Emile Alghoul, Rania Ghouil, Claire Friel, Didier Busso, Juan C Cañas, François-Xavier Theillet, Romain Le Bars, Aura Carreira, Angelos Constantinou, Jihane Basbous, Sophie Zinn-Justin.
      During mitosis, the microtubule depolymerase KIF2C, the tumor suppressor BRCA2, and the kinase PLK1 contribute to the control of kinetochore-microtubule attachments. Both KIF2C and BRCA2 are phosphorylated by PLK1, and BRCA2 phosphorylated at T207 (BRCA2-pT207) serves as a docking site for PLK1. Reducing this interaction results in unstable microtubule-kinetochore attachments. Here we identified that KIF2C also directly interacts with BRCA2-pT207. Indeed, the N-terminal domain of KIF2C adopts a Tudor/PWWP/MBT fold that unexpectedly binds to phosphorylated motifs. Using an optogenetic platform, we found that KIF2C forms membrane-less organelles that assemble through interactions mediated by this phospho-binding domain. KIF2C condensation does not depend on BRCA2-pT207 but requires active Aurora B and PLK1 kinases. Moreover, it concentrates PLK1 and BRCA2-pT207 in an Aurora B-dependent manner. Finally, KIF2C depolymerase activity promotes the formation of KIF2C condensates, but strikingly, KIF2C condensates exclude tubulin: they are located on microtubules, especially at their extremities. Altogether, our results suggest that, during the attachment of kinetochores to microtubules, the assembly of KIF2C condensates amplifies PLK1 and KIF2C catalytic activities and spatially concentrates BRCA2-pT207 at the extremities of microtubules. We propose that this novel and highly regulated mechanism contributes to the control of microtubule-kinetochore attachments, chromosome alignment, and stability.
    DOI:  https://doi.org/10.1093/nar/gkaf476
  6. bioRxiv. 2025 Jun 03. pii: 2025.06.03.657645. [Epub ahead of print]
    Orderly mitosis shapes interphase genome architecture.
    Krishnendu Guin, Adib Keikhosravi, Gianluca Pegoraro, Raj Chari, Tom Misteli.
      Genomes assume a complex 3D architecture in the interphase cell nucleus. Yet, the molecular mechanisms that determine global genome architecture are only poorly understood. To identify mechanisms of higher order genome organization, we performed high-throughput imaging-based CRISPR knockout screens targeting 1064 genes encoding nuclear proteins in human cell lines. We assessed changes in the distribution of centromeres at single cell resolution as surrogate markers for global genome organization. The screens revealed multiple major regulators of spatial distribution of centromeres including components of the nucleolus, kinetochore, cohesins, condensins, and the nuclear pore complex. Alterations in centromere distribution required progression through the cell cycle and acute depletion of mitotic factors with distinct functions altered centromere distribution in the subsequent interphase. These results identify molecular determinants of spatial centromere organization, and they show that orderly progression through mitosis shapes interphase genome architecture.
    DOI:  https://doi.org/10.1101/2025.06.03.657645
  7. Cells. 2025 May 26. pii: 784. [Epub ahead of print]14(11):
    The stn1-sz2 Mutant Provides New Insight into the Impacts of Telomeric Cdc13-Stn1-Ten1 Dysfunction on Cell Cycle Progression.
    Nathalie Grandin, Michel Charbonneau.
      The conserved and essential Cdc13/CTC1-Stn1-Ten1 telomeric complex (CST) ensures chromosome stability by protecting telomere ends and regulating telomerase accessibility. In a recent study, we uncovered mutants of the S. cerevisiae CST, in which damage was sensed by the two major G2/M spindle checkpoints (one is Bub2-dependent and the other one Mad2-dependent), as well as the major G2/M DNA damage checkpoint (Mec1-dependent). In this study, we found, by fluorescence microscopy, that the stability of the mitotic tubulin spindle was profoundly affected in the best-studied of these mutants, stn1-sz2. Additional data from genetic analyses suggested the potential involvement of Stu1 and Stu2, as well as Slk19, in these defects. Throughout this study, we compared the phenotypes of stn1-sz2 with those of cdc13-1, the best-studied CST mutant, which also serves as a prototype of telomere-damage-characterized CST mutants. We propose that stn1-sz2 represents the prototype of cst mutants characterized by tubulin spindle damage. These newly described phenotypes potentially represent the basis for identifying new functions of the CST telomeric complex. These functions might consist of ensuring correct chromosome segregation through the stabilization of the mitotic spindle.
    Keywords:  Bub2 and Mad2 spindle checkpoints; Cdc13-Stn1-Ten1 complex; Mec1 DNA damage checkpoint; budding yeast telomeres; cell cycle
    DOI:  https://doi.org/10.3390/cells14110784
  8. J Cell Biol. 2025 Jul 07. pii: e202504075. [Epub ahead of print]224(7):
    Mitotic genome folding.
    Tatsuya Hirano.
      Mitotic genome folding, or mitotic chromosome assembly, is essential for the faithful segregation of genetic information into daughter cells. While this process was once thought to be highly complex, requiring a myriad of protein components, recent studies have begun to revise this conventional view. An emerging view is that the core reaction of mitotic genome folding is mediated by a dynamic interplay of a limited number of structural components, namely, condensins, topoisomerase II (topo II), and histones. Condensins and topo II are two distinct classes of ATPases that cooperate to actively form and manipulate DNA loops, both accumulating at the central axial regions of the resulting chromosomes. In contrast, nucleosomes and linker histones help to compact DNA loops by cooperating and competing with the action of these ATPases. In this review, I will focus on the recent advances in the field, with an emphasis on the mechanistic aspects of mitotic genome folding.
    DOI:  https://doi.org/10.1083/jcb.202504075
  9. bioRxiv. 2025 Jun 08. pii: 2025.06.05.658139. [Epub ahead of print]
    Identification of chromatin-associated RNAs at human centromeres.
    Kelsey Fryer, Charles Limouse, Aaron F Straight.
      Centromeres are a specialized chromatin domain that are required for the assembly of the mitotic kinetochore and the accurate segregation of chromosomes. Non-coding RNAs play essential roles in regulating genome organization including at the unique chromatin environment present at human centromeres. We performed Chromatin-Associated RNA sequencing (ChAR-seq) in three different human cell lines to identify and map RNAs associated with centromeric chromatin. Centromere enriched RNAs display distinct contact behaviors across repeat arrays and generally belong to three categories: centromere encoded, nucleolar localized, and highly abundant, broad-binding RNAs. Most centromere encoded RNAs remain locally associated with their transcription locus with the exception of a subset of human satellite RNAs. This work provides a comprehensive identification of centromere bound RNAs that may regulate the organization and activity of the centromere.
    DOI:  https://doi.org/10.1101/2025.06.05.658139
  10. Genome Res. 2025 Jun 06. pii: gr.280648.125. [Epub ahead of print]
    Mitotic chromosomes harbor cell type and species-specific structural features within a universal loop array conformation.
    Marlies E Oomen, A Nicole Fox, Inma Gonzalez, Amandine Molliex, Thaleia Papadopoulou, Pablo Navarro, Job Dekker.
      Mitotic chromosomes are considered to be universally folded as loop arrays across species and cell types. However, some studies suggest that features of mitotic chromosomes might be cell type or species specific. We previously reported that CTCF binding in human differentiated cell lines is lost in mitosis, whereas mitotic mouse embryonic stem cells (mESC) display prominent binding at a subset of CTCF sites. Here, we perform footprint ATAC-seq analyses of mESCs and somatic mouse and human cells confirming these findings. We then investigate roles of mitotically bookmarked CTCF in prometaphase chromosome organization by Hi-C. We do not find any remaining interphase structures such as TADs or loops at bookmarked CTCF sites in mESCs. This suggests that mitotic loop extruders condensin I and II are not blocked by CTCF, and thus that maintained CTCF binding does not alter mitotic chromosome folding. Lastly, we compare mitotic Hi-C data generated in this study in mouse with public data in human and chicken. We do not find any cell type-specific differences; however, we find a difference between species. The average genomic size of mitotic loops is smaller in chicken (200-300 kb), compared to human (400-600 kb) and especially mouse (1-1.5 mb). Interestingly, we find that this difference is correlated with the genomic length of q-arms in these species, a finding we confirm by microscopy measurements of chromosome compaction. This suggests that the dimensions of mitotic chromosomes can be modulated through control of loop size by condensins to facilitate species-appropriate shortening of chromosome arms.
    DOI:  https://doi.org/10.1101/gr.280648.125
  11. bioRxiv. 2025 May 28. pii: 2025.05.23.655122. [Epub ahead of print]
    Replication stress alters CENP-A nucleosome stability during S phase.
    Alexander S Lee, Che-Fan Huang, Taojunfeng Su, Justin Bodner, Neil L Kelleher, Daniel R Foltz.
      1.The maintenance of centromere identity is essential for the proper segregation of chromosomes during cell division. Centromere identity is epigenetically specified by centromeric histone H3 variant CENP-A, and its retention during DNA replication is facilitated by HJURP chaperone. Replication stress disrupts replication fork progression and can negatively influence the interactions between histone chaperone network necessary for retention and deposition of parental and new histones, respectively. In this study we investigate the role of replication stress response on centromere inheritance. We define changes in centromere-associated proteins that govern stability of centromeric and canonical nucleosomes through proximity labeling coupled with affinity purification mass spectrometry. We identified that under replication stress, CENP-A-containing chromatin strongly enriches for SWI/SNF chromatin remodeling proteins ATRX. We show that depletion of ATRX and its associated histone H3.3 chaperone DAXX results in the loss CENP-A retention in S-phase and loss persists into the subsequent cell cycle. Altogether our findings provide insight into how replication stress negatively influences centromeric chromatin instability and delineates a function of DAXX-ATRX complex in maintaining centromere inheritance during DNA replication.
    DOI:  https://doi.org/10.1101/2025.05.23.655122
  12. bioRxiv. 2025 Jun 06. pii: 2025.06.05.657915. [Epub ahead of print]
    Mechanical force locally damages, remodels and stabilizes the lattice of spindle microtubules.
    Caleb J Rux, Megan K Chong, Sean Myers, Nathan H Cho, Sophie Dumont.
      To segregate chromosomes at cell division, the spindle must maintain its structure under force. How it does so remains poorly understood. To address this question, we use microneedle manipulation to apply local force to spindle microtubule bundles, kinetochore-fibers (k-fibers), inside mammalian cells. We show that local load directly fractures k-fibers, and that newly created plus-ends often have arrested dynamics, resisting depolymerization. Force alone, without fracture, is sufficient for spindle microtubule stabilization, as revealed by laser ablating k-fibers under local needle force. Doublecortin, which binds a compacted microtubule lattice, is lost around the force application site, suggesting local force-induced structural remodeling. In turn, EB1, which recognizes GTP-tubulin, is locally enriched at stabilization sites, both before and after force-induced fracture. Together, our findings support a model where force-induced damage leads to local spindle microtubule lattice remodeling and stabilization, which we propose reinforces the spindle where it experiences critical loads.
    DOI:  https://doi.org/10.1101/2025.06.05.657915
  13. Biol Cell. 2025 Jun;117(6): e70015
    An Auxin Inducible Degradation System to Study Mklp2 Functions in MDCK Epithelial Cells.
    Morgane Rodriguez, Valérie Simon, Bénédicte Delaval, Benjamin Vitre.
      The auxin inducible degradation (AID) system, which allows for rapid and inducible degradation of a protein of interest, is an efficient technology to study protein function in cells. This system proves particularly useful to study cellular motors that can be involved in different mechanisms depending on the cell cycle stage. Mitotic kinesin-like protein 2 (Mklp2) is a member of the kinesin-6 family involved in intracellular trafficking both in interphase and mitosis. In mitosis, at anaphase onset, it relocates the chromosomal passenger complex (CPC), from the chromatin to the spindle midzone and equatorial cortex. Inhibition or knockdown of Mklp2 therefore leads to CPC re-localization defects and cytokinesis failure. Existing tools used to study Mklp2 functions in cells, including antibodies, siRNA, and small molecule inhibitors, allowed the identification of the general function of Mklp2 in mitosis. However, these tools induce different intermediate phenotypes during the course of mitosis, highlighting the need for an alternative Mklp2 perturbation approach. We report here a new tool to study the discrete localization of endogenous Mklp2 at different stages of the cell cycle combined with an AID tag that allows the study of the kinesin with high specificity, high efficiency, and high temporal resolution in MDCK (Madin-Darby canine kidney) epithelial cells. We show that upon auxin treatment, the acute and rapid degradation of Mklp2 results in delayed re-localization of CPC component Aurora-B to the spindle midzone during anaphase, cytokinesis failure, and cell binucleation. We validate the specificity of the system by rescuing Mklp2 expression and reversing the phenotypes. Overall, this new tool facilitates the study of endogenous Mklp2 localization and function at specific stages of the cell cycle and offers a highly specific method for exploring its roles in a nontransformed mammalian model cell line widely used to study epithelial organization and dynamics.
    DOI:  https://doi.org/10.1111/boc.70015
  14. Cytoskeleton (Hoboken). 2025 Jun 11.
    Making Two out of One: Kinesin Motors Driving Plant Cell Division.
    Choy Kriechbaum, Sabine Müller.
      The Kinesin superfamily of microtubule dependent motors is present in all eukaryotes. Not all of the subfamilies are represented in all kingdoms, and the ones that are do not always show conserved functions. Tight control of the cytoskeleton is essential for proper progression and completion of mitosis and cytokinesis, and key functions are carried out by kinesin motor proteins of various families. In this context, we take a closer look at plant kinesins involved in spindle formation and chromosome congression. Additionally, plant kinesins have been implicated in the deposition of cell plate material in the plane of cell division during cytokinesis in the angiosperm Arabidopsis thaliana and the moss Physcomitrium patens. In light of these recent discoveries, this mini-review aims to give an update on kinesins involved in plant cell division with brief reference to well-studied counterparts in other organisms.
    Keywords:  cell division; kinesin; phragmoplast; plant; spindle
    DOI:  https://doi.org/10.1002/cm.22050
  15. Mechanobiol Med. 2025 Jun;3(2): 100135
    Mechanosensitive nuclear checkpoint: nuclear envelope as a sensor of chromosomal instability and driver of cell fate.
    Chenyang Ji, Junwei Chen, Fuxiang Wei.
      The nuclear envelope (NE) is a dynamic, mechanosensitive structure that functions as a protective barrier for the genome and serves as a checkpoint responding to external stimuli. It plays a critical role in maintaining genomic stability and regulating cell fate. This review synthesizes recent research highlighting the role of NE as a mechanical checkpoint in ensuring accurate chromosome segregation, regulating cell cycle progression, and contributing to cancer development. Chromosome mis-segregation during cell division is a major driver of aneuploidy, a condition closely associated with genomic instability and cellular transformation. The role of NE in chromatin organization and gene expression regulation is also discussed, underscoring its importance in cell differentiation and identity.
    Keywords:  Cell cycle; Chromatin; Gene expression; Mechanosensitive checkpoint; Nuclear envelope
    DOI:  https://doi.org/10.1016/j.mbm.2025.100135
  16. Dev Dyn. 2025 Jun 12.
    Differential sensitivity of midline development to mitosis during and after primitive streak extension.
    Zhiling Zhao, Rieko Asai, Takashi Mikawa.
       BACKGROUND: Midline establishment is a fundamental process during early embryogenesis for Bilaterians. Midline morphogenesis in non-amniotes can occur without mitosis, through Planar Cell Polarity (PCP) signaling. By contrast, amniotes utilize both cellular processes for developing the early midline landmark, the primitive streak (PS). This study focused on the role of cell proliferation for midline development at pre- and post-PS-extension stages and analyzed PCP signaling components at post-PS-extension stages.
    RESULTS: In contrast to pre-PS-extension stages, embryos under mitotic arrest during the post-PS-extension preserved notochord (NC) extension and Hensen's node (HN)/PS regression judged by both morphology and marker genes; although they became shorter, their lengths remained proportional to the embryo length. Laterality and segmentation of paraxial mesoderm were lost upon mitotic arrest. Accompanied by mitotic arrest-induced embryonic size reduction, cells including midline tissue displayed hypertrophy.
    CONCLUSION: This study has identified at least two distinct mitosis sensitivity phases during early midline development: One is PS extension that requires both mitosis and PCP, and the other is mitotic arrest-resistant midline development at post-PS-extension stages, with a still undefined influence by PCP signaling components.
    Keywords:  PCP; cell hypertrophy; cell proliferation; embryo size; midline patterning; notochord; primitive streak
    DOI:  https://doi.org/10.1002/dvdy.70045
  17. J Cell Sci. 2025 Jun 12. pii: jcs.264015. [Epub ahead of print]
    CLASP1 regulates Dynein for PLK1-mediated spindle organization and cytokinesis in oocyte meiosis.
    Meng-Meng Shan, Ping-Shuang Lu, Yuan-Jing Zou, Kun-Huan Zhang, Jing-Cai Liu, Jia-Qian Ju, Shao-Chen Sun.
      The meiotic spindle organization and cytokinesis are important for mammalian oocyte maturation. CLIP-associating protein (CLASP) 1 is a member of microtubule plus-end binding proteins, which is reported to regulate cytokinesis in mitosis; however, the functions of CLASP1 in meiosis are still unclear. In this study, we reported that CLASP1 played critical roles both at metaphase and telophase in mouse oocyte meiosis. Our results indicated that CLASP1 was essential for oocyte maturation and its depletion caused the spindle organization and microtubule-kinetochore attachment defects at metaphase Ⅰ, while this might be due to its association with PLK1/p-MAPK. Besides, deacetylases HDAC6/ SIRT1 were found to be decreased which further affected tubulin acetylation level and microtubule stability after CLASP1 depletion. We also showed that CLASP1 could associate with PLK1/PRC1-based central spindle formation and cytokinesis at telophase Ⅰ. Moreover, Dynein was recognized to interact closely with CLASP1 and may function as a downstream motor protein involved in the orderly transport of PLK1. Taken together, we demonstrated that CLASP1 may play multiple roles in Dynein-based PLK1 for spindle organization and cytokinesis in mouse oocyte meiosis.
    Keywords:  Cytokinesis; Meiosis; Oocyte; Spindle; Tubulin acetylation
    DOI:  https://doi.org/10.1242/jcs.264015
  18. Chromosome Res. 2025 Jun 12. 33(1): 11
    Solution conformational differences between conventional and CENP-A nucleosomes are accentuated by reversible deformation under high pressure.
    Kushol Gupta, Nikolina Sekulić, Praveen Kumar Allu, Nicklas Sapp, Qingqiu Huang, Kathryn Sarachan, Mikkel Christensen, Reidar Lund, Susan Krueger, Joseph E Curtis, Richard E Gillilan, Gregory D Van Duyne, Ben E Black.
      Solution-based interrogation of the physical nature of nucleosomes has its roots in X-ray and neutron scattering experiments, including those that provided the initial observation that DNA wraps around core histones. In this study, we performed a comprehensive small-angle scattering study to compare canonical nucleosomes with variant centromeric nucleosomes harboring the histone variant, CENP-A. We used nucleosome core particles (NCPs) assembled on an artificial positioning sequence (Widom 601) and compared these to those assembled on a natural α-satellite DNA from human centromeres. We establish the native solution properties of octameric H3 and CENP-A NCPs using analytical ultracentrifugation (AUC), small-angle X-ray scattering (SAXS), and contrast variation small-angle neutron scattering (CV-SANS). Using high-pressure SAXS (HP-SAXS), we discovered that both histone and DNA sequence have an impact on the stability of octameric nucleosomes in solution under high pressure (300 MPa), with evidence of reversible unwrapping in these experimental conditions. Both canonical nucleosomes harboring conventional histone H3 and their centromeric counterparts harboring CENP-A have a substantial increase in their radius of gyration, but this increase is much less prominent for centromeric nucleosomes. More broadly for chromosome-related research, we note that as HP-SAXS methodologies expand in their utility, we anticipate this will provide a powerful solution-based approach to study nucleosomes and higher-order chromatin complexes.
    Keywords:  Analytical ultracentrifugation; Centromeres; High-pressure; Nucleosome; Small-angle X-ray scattering; Small-angle neutron scattering
    DOI:  https://doi.org/10.1007/s10577-025-09769-z
  19. bioRxiv. 2025 May 29. pii: 2025.05.28.656693. [Epub ahead of print]
    AURKA inhibition amplifies DNA replication stress to foster WEE1 kinase dependency and synergistic antitumor effects with WEE1 inhibition in cancers.
    Jong Woo Lee, Jackie Shi, Julian Barrantes, Pratima Chaurasia, Sundong Kim, Sebastian Cruz-Gomez, Cindy Yang, Jianlei Gu, Hongyu Zhao, Dejian Zhao, Benjamin Schiff, Ansley Roche, Elizabeth B Perry, Jeffrey P Townsend, Gary M Kupfer, Katerina Politi, Erica Golemis, Barbara Burtness.
      Highly elevated expression of the oncogene Aurora kinase A (AURKA) occurs in numerous human cancers harboring defective p53, nominating AURKA as a potential vulnerability in TP53 -mutated cancer. However, clinical trials have indicated modest monotherapy activity of AURKA inhibitors. Here, we demonstrate that AURKA inhibition promotes phosphorylation of Replication Protein A (RPA), resulting in stalled DNA replication fork progression and eliciting a replication stress response in multiple TP53 -mutated models, creating a druggable dependence on the mitotic checkpoint kinase WEE1. Combined inhibition of AURKA and WEE1 synergistically enhanced replication stress, tumor-specific apoptotic cell death, and mitotic catastrophe, and lead to marked tumor regression in cell line- and patient-derived xenograft models of TP53 -mutated cancer. Our findings define enhanced DNA replication stress as underlying the strong synergy between AURKA and WEE1 inhibitors and offer preclinical confirmation of efficacy, indicating high potential for clinical translation of this synthetic lethal strategy for TP53 -mutated carcinomas.
    Statement of significance: We demonstrate that a small molecule AURKA inhibitor amplifies DNA replication stress in TP53 -mutated carcinomas. This amplification of DNA replication stress can be leveraged this for synthetic lethal therapy in a combination with WEE1 inhibition that enhances antitumor effects in in vitro , in xenografts and in patient-derived xenograft models, advancing a promising novel combination therapy.
    DOI:  https://doi.org/10.1101/2025.05.28.656693
  20. Cell Biosci. 2025 Jun 07. 15(1): 81
    Cilia at the crossroad: convergence of regulatory mechanisms to govern cilia dynamics during cell signaling and the cell cycle.
    Lukáš Čajánek, Sindija Smite, Olha Ivashchenko, Martina Huranova.
      Cilia are versatile, microtubule-based organelles that facilitate cellular signaling, motility, and environmental sensing in eukaryotic cells. These dynamic structures act as hubs for key developmental signaling pathways, while their assembly and disassembly are intricately regulated along cell cycle transitions. Recent findings show that factors regulating ciliogenesis and cilia dynamics often integrate their roles across other cellular processes, including cell cycle regulation, cytoskeletal organization, and intracellular trafficking, ensuring multilevel crosstalk of mechanisms controlling organogenesis. Disruptions in these shared regulators lead to broad defects associated with both ciliopathies and cancer. This review explores the crosstalk of regulatory mechanisms governing cilia assembly, disassembly, and maintenance during ciliary signaling and the cell cycle, along with the broader implications for development, tissue homeostasis, and disease.
    Keywords:  Cancer; Cell cycle regulation; Cilia; Ciliary dynamics; Ciliary signaling; Ciliopathies; Tissue development
    DOI:  https://doi.org/10.1186/s13578-025-01403-z
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