bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2025–08–10
sixteen papers selected by
Valentina Piano, Uniklinik Köln
  1. Dynamin regulates PLK-1 localization and spindle pole assembly during mitosis.
  2. Discovery of unique mitotic mechanisms in Paradiplonema papillatum.
  3. Global inhibition of deadenylation stabilizes the transcriptome in mitotic cells.
  4. Ubiquitin specific protease 7 deubiquitinates and regulates Aurora B-mediated cytokinesis.
  5. Effects of chromosome number reduction on mitotic and meiotic stability in fission yeast.
  6. Coiled-coil interactions drive ectopic condensation of overexpressed MAD1 to promote mitotic slippage in cancer cells.
  7. NuMA mechanically reinforces the spindle independently of its partner dynein.
  8. Calyculin A Induces Premature Chromosome Condensation and Chromatin Compaction in G 1 -Phase HeLa Cells without Histone H1 Phosphorylation.
  9. Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation.
  10. Mitotic entry is controlled by the plant-specific phosphatase BSL1 and cyclin-dependent kinase B.
  11. Tethered to survive: Mitotic transcription secures faithful inheritance of extrachromosomal DNA.
  12. Interaction of IRS2 with PLK1 protects cells from mitotic stress.
  13. Basal Cell-Contact Dynamics Influence Tissue Packing in a Proliferating Mammalian Epithelium.
  14. Unequal segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in sister cells in vivo.
  15. Arp2/3 and type-I myosins control chromosome mobility and end-resection at double-strand breaks in S. cerevisiae.
  16. Single-cell multiomics reveals the oscillatory dynamics of mRNA metabolism and chromatin accessibility during the cell cycle.
  1. bioRxiv. 2025 Jul 21. pii: 2025.07.21.665896. [Epub ahead of print]
    Dynamin regulates PLK-1 localization and spindle pole assembly during mitosis.
    Carter Dierlam, Livinus Anyanwu, Stephanie Held, Robert H Newman, Jyoti Iyer.
      Accurate cytokinesis is essential for maintaining genomic integrity. Although the GTPase dynamin has been well studied for its role in vesicular trafficking, its function during mitosis remains poorly understood. In this study, we uncover a novel role for the C. elegans dynamin homolog, DYN-1, in regulating mitotic spindle pole assembly and the spatiotemporal localization of the key mitotic kinase Polo-like kinase 1 (PLK-1). Our studies demonstrate that the depletion of DYN-1 leads to enlarged metaphase spindle poles and elevated levels of centrosome-associated PLK-1. Strikingly, PLK-1 fails to re-localize from centrosomes to the midbody during late mitosis in a subset of DYN-1-depleted embryos, correlating with abnormal PLK-1 localization at the midbody and defective midbody formation. Importantly, this phenotype is likely not due to increased total PLK-1 protein levels, as DNM2 (human homolog of DYN-1) depletion in HeLa cells did not alter total Plk1 abundance. Together, our findings identify DYN-1 as a new regulator of PLK-1 localization during mitosis and suggest that failure to remove PLK-1 from centrosomes may underlie cytokinesis defects that are observed upon DYN-1 depletion.
    SIGNIFICANCE STATEMENT: Dynamin is primarily known for its function in endocytosis, but its involvement in mitosis is not well defined. This study shows that dynamin helps organize the mitotic spindle and ensures proper localization of the master mitotic kinase PLK-1 in C. elegans embryos. These findings reveal a previously unrecognized role for dynamin in mitosis and suggest new links between membrane dynamics and the cell division machinery.
    DOI:  https://doi.org/10.1101/2025.07.21.665896
  2. Open Biol. 2025 Aug;15(8): 250096
    Discovery of unique mitotic mechanisms in Paradiplonema papillatum.
    Bungo Akiyoshi, Drahomíra Faktorová, Julius Lukeš.
      Diplonemids are highly diverse and abundant marine plankton with significant ecological importance. However, little is known about their biology, even in the model diplonemid Paradiplonema papillatum whose genome sequence is available. Examining the subcellular localization of proteins using fluorescence microscopy is a powerful approach to infer their putative function. Here, we report a plasmid-based method that enables YFP-tagging of a gene at the endogenous locus. By examining the localization of proteins whose homologs are involved in chromosome organization or segregation in other eukaryotes, we discovered several notable features in mitotically dividing P. papillatum cells. Cohesin is enriched on condensed interphase chromatin. During mitosis, chromosomes organize into two rings (termed mitotic rings herein) that surround the elongating nucleolus and align on a bipolar spindle. Homologs of chromosomal passenger complex components (INCENP, two Aurora kinases and KIN-A), a CLK1 kinase, meiotic chromosome axis protein SYCP2L1, spindle checkpoint protein Mad1 and microtubule regulator XMAP215 localize in between the two mitotic rings. In contrast, a Mad2 homolog localizes near basal bodies as in trypanosomes. By representing the first molecular characterization of mitotic mechanisms in P. papillatum and raising many questions, this study forms the foundation for dissecting mitotic mechanisms in diplonemids.
    Keywords:  Euglenozoa; chromosome; diplonemid; kinetochore; kinetoplastid
    DOI:  https://doi.org/10.1098/rsob.250096
  3. bioRxiv. 2025 Jul 22. pii: 2025.07.22.666109. [Epub ahead of print]
    Global inhibition of deadenylation stabilizes the transcriptome in mitotic cells.
    Ekaterina Khalizeva, Arash Latifkar, David P Bartel, Jimmy Ly, Iain M Cheeseman.
      In the presence of cell division errors, mammalian cells can pause in mitosis for tens of hours with little to no transcription, while still requiring continued translation for viability. These unique aspects of mitosis require substantial adaptations to the core gene expression programs. Indeed, during interphase, the homeostatic control of mRNA levels involves a constant balance of transcription and degradation, with a median mRNA half-life of ∼2-4 hours. If such short mRNA half-lives persisted in mitosis, cells would be expected to quickly deplete their transcriptome in the absence of new transcription. Here, we report that the transcriptome is globally stabilized during prolonged mitotic delays. Typical mRNA half-lives are increased >4-fold in mitosis compared to interphase, thereby buffering mRNA levels in the absence of new synthesis. Moreover, the poly(A)-tail-length profile of mRNAs changes in mitosis, strongly suggesting a mitotic repression of deadenylation. We further show that mRNA stabilization in mitosis is dependent on cytoplasmic poly(A)-binding proteins PABPC1&4. Depletion of PABPC1&4 disrupts the maintenance of mitotic arrest, highlighting the critical physiological role of mitotic transcriptome buffering.
    Highlights: The cellular transcriptome is globally stabilized during prolonged mitotic arrestDistinct poly(A)-tail-length profile of mRNAs in mitosis suggests repression of deadenylationmRNA stabilization in mitosis is dependent on PABPC1 and PABPC4Degradation of mRNAs during mitosis compromises maintenance of mitotic arrest.
    DOI:  https://doi.org/10.1101/2025.07.22.666109
  4. BMB Rep. 2025 Aug 04. pii: 6359. [Epub ahead of print]
    Ubiquitin specific protease 7 deubiquitinates and regulates Aurora B-mediated cytokinesis.
    Kamini Kaushal, Ainsley Mike Antao, Soumyadip Das, Sammy L Kim, Girish Birappa, Sripriya Rajkumar, D A Ayush Gowda, C Bindu Ajaykumar, Vijai Singh, Keesung Kim, Bharathi Suresh, Suresh Ramakrishna.
      Aurora B is a widely studied mitotic checkpoint kinase that forms a part of the chromosomal passenger complex. The entry to and exit from mitosis are exquisitely controlled by Aurora B proteins, which regulate mitotic phases including chromosomal condensation, segregation, and cytokinesis, ensuring faithful propagation of daughter cells. Abnormal regulation of Aurora B proteins during the cell cycle can cause increased chromosomal segregation errors and ultimately lead to cancer. Thus, it is important to understand the key mechanisms that can modulate Aurora B protein levels during the cell cycle. Therefore, in this study we demonstrated the role of Ubiquitin-specific protease 7 (USP7) in regulating Aurora B protein level. Aurora B protein levels are upregulated when USP7 is dose-dependently increased, and downregulated when USP7 is depleted. By co-immunoprecipitation and Duolink assays, we demonstrated that USP7 interact with Aurora B. Furthermore, by treating cycloheximide we showed that USP7 extends the Aurora B protein half-life by its deubiquitinating activity. Finally, CRISPR/Cas9-mediated USP7 knockout produces severe nuclear structural defects causing multi-nucleation and cytokinesis failures, suggesting that the important role of USP7 during mitotic progression in stabilizing Aurora B.
  5. Genome Biol. 2025 Aug 04. 26(1): 232
    Effects of chromosome number reduction on mitotic and meiotic stability in fission yeast.
    Yueyue Jiang, Yanze Jian, Lingyun Nie, Xin Gu, Ziyi Lu, Yongkang Chu, Xing Liu, Xuebiao Yao, Jin-Qiu Zhou, Shengnan Zheng, Chuanhai Fu.
       BACKGROUND: Genetic information is stored on multiple chromosomes in eukaryotic organisms and is passed on to offspring through cell division. How chromosome number influences cell division and chromosome segregation is not yet understood.
    RESULTS: In this study, we use artificial chromosome-fusion fission yeast cells, which contain one or two chromosomes, as models to investigate the effects of a reduced chromosome number on mitosis and meiosis. In mitosis, chromosome number reduction, particularly full fusion into one chromosome, prolongs mitotic duration in a manner dependent on the spindle assembly checkpoint and improves chromosome segregation accuracy in spindle assembly checkpoint-deficient cells. By contrast, in meiosis, chromosome number reduction impairs prophase oscillatory nuclear movement, prolongs meiosis I duration but shortens meiosis II duration, and severely compromises meiosis I chromosome segregation.
    CONCLUSIONS: Our work uncovers different effects of reduced chromosome number on mitotic and meiotic stability and offers insights into how organisms may select the appropriate number of chromosomes in evolution.
    Keywords:  Chromosome number; Fission yeast; Meiosis; Mitosis; Spindle assembly checkpoint
    DOI:  https://doi.org/10.1186/s13059-025-03704-5
  6. bioRxiv. 2025 Jul 31. pii: 2025.07.29.667513. [Epub ahead of print]
    Coiled-coil interactions drive ectopic condensation of overexpressed MAD1 to promote mitotic slippage in cancer cells.
    Jason Tones, Jasper Jeffrey, Rachel M Lackner, David M Chenoweth, Huaiying Zhang.
      The mitotic checkpoint protein MAD1 is significantly overexpressed in several cancers, weakening the checkpoint and promoting mitotic slippage. Overexpressed MAD1 forms ectopic foci in mitotic cells, yet the biophysical nature of these foci and their contributions to mitotic slippage remain unclear. Here, we report that MAD1 foci are phase-separated condensates that shorten the mitotic duration by sequestering checkpoint proteins. Our biophysical quantifications reveal that MAD1 ectopic foci in mitotic cells exhibit dynamic condensate properties rather than those of a solid aggregate. Using an inducible phase separation assay in live cells, we show that MAD1 phase separation is driven by interactions between its coiled-coil and disordered domains at the N-terminus. We decouple the contributions of condensation from concentration by inducing the formation of MAD1 ectopic condensates in mitotic cells with low levels of MAD1, demonstrating that the condensation process directly drives mitotic slippage. Mechanistically, the MAD1 ectopic condensate traps the diffusive pool of MAD2, an interaction partner of MAD1, thereby weakening the MAD2 conversion cycle necessary for a robust mitotic checkpoint. Our work illustrates a loss of function caused by ectopic condensates in MAD1-overexpressed cancer cells.
    DOI:  https://doi.org/10.1101/2025.07.29.667513
  7. Curr Biol. 2025 Jul 30. pii: S0960-9822(25)00894-2. [Epub ahead of print]
    NuMA mechanically reinforces the spindle independently of its partner dynein.
    Nathan H Cho, Merve Aslan, Aryan Taheri, Ahmet Yildiz, Sophie Dumont.
      During cell division, both motor and non-motor proteins organize microtubules to build the spindle and maintain it against opposing forces. Nuclear mitotic apparatus (NuMA), a long microtubule-binding protein, is essential to spindle structure and function. NuMA recruits the motor dynein to actively cluster spindle microtubule minus-ends, but whether NuMA performs other spindle roles remains unknown. Here, we show that NuMA acts independently of dynein to passively reinforce the mammalian spindle. NuMA that cannot bind dynein is sufficient to protect spindle poles against fracture under external force. In contrast, NuMA with a shorter coiled coil or disrupted self-interactions cannot protect spindle poles, and NuMA turnover differences cannot explain mechanical differences. In vitro, NuMA's C terminus self-interacts and bundles microtubules without dynein, dependent on residues essential to pole protection in vivo. Together, this suggests that NuMA reinforces spindle poles by crosslinking microtubules, using its long coiled coil and self-interactions to reach multiple, far-reaching pole microtubules. We propose that NuMA acts as a mechanical "multitasker" targeting contractile motor activity and separately crosslinking microtubules, with both functions synergizing to drive spindle mechanical robustness.
    Keywords:  NuMA; crosslinking; dynein; force; mechanics; microtubules; pole; robustness; self-organization; spindle
    DOI:  https://doi.org/10.1016/j.cub.2025.07.028
  8. bioRxiv. 2025 Jul 21. pii: 2025.07.16.665228. [Epub ahead of print]
    Calyculin A Induces Premature Chromosome Condensation and Chromatin Compaction in G 1 -Phase HeLa Cells without Histone H1 Phosphorylation.
    Natalia Y Kochanova, Matthieu Vermeren, Bram Prevo, Ipek Ustun, Shaun Webb, Linfeng Xie, William C Earnshaw, James R Paulson.
      We show here that treatment of HeLa cells with calyculin A, an inhibitor of Protein Phosphatases 1 and 2A, induces premature chromosome condensation (PCC) at any point in interphase of the cell cycle. Chromosomes in G 1 -phase PCC closely resemble metaphase chromatids in the light microscope, and measurements using FLIM-FRET show that they have the same level of chromatin compaction as metaphase chromosomes. However, histone H1 is not phosphorylated in G 1 - or early S-phase PCC. These results suggest that H1 phosphorylation is not required for mitotic chromosome condensation and chromatin compaction. They also confirm that Cdk1/cyclin B, which directly phosphorylates histone H1, is not active in G 1 and thus is not essential for G 1 - PCC. We suggest that induction of G 1 -PCC involves protein kinases or other factors that are either held in an inactive state by protein phosphatases, or constitutively active but countered by phosphatases. The same factors may be involved in the onset of normal mitosis, becoming active when protein phosphatases are downregulated. Induction of PCC with calyculin A should provide a useful system for identifying and studying the biochemical pathways that are required for mitotic chromosome compaction, nuclear envelope breakdown, and other events of mitosis.
    DOI:  https://doi.org/10.1101/2025.07.16.665228
  9. bioRxiv. 2025 Jul 28. pii: 2025.07.23.666394. [Epub ahead of print]
    Maternal CENP-C restores centromere symmetry in mammalian zygotes to ensure proper chromosome segregation.
    Catherine A Tower, Gabriel Manske, Emily L Ferrell, Dilara N Anbarci, Kelsey Jorgensen, Binbin Ma, Mansour Aboelenain, Rajesh Ranjan, Saikat Chakraborty, Lindsay Moritz, Arunika Das, Michele Boiani, Ben E Black, Shawn Chavez, Erica E Marsh, Ariella Shikanov, Karen Schindler, Xin Chen, Saher Sue Hammoud.
      Across metazoan species, the centromere-specific histone variant CENP-A is essential for accurate chromosome segregation, yet its regulation at the parental-to-zygote transition in mammals is poorly understood. To address this, we developed a CENP-A-mScarlet knock-in mouse model, which revealed sex-specific dynamics: mature sperm retains 10% of the CENP-A levels present in MII-oocytes. However, in zygotes prior to the first mitosis, this difference is resolved, using maternally inherited cytoplasmic-CENP-A. Notably, the increase in CENP-A at paternal centromeres is independent of sensing CENP-A asymmetry or the presence of maternal chromosomes. Instead, CENP-A equalization relies on asymmetric recruitment of maternal CENP-C to paternal centromeres. Depletion of maternal CENP-A decreases total CENP-A in pronuclei without disrupting equalization. In contrast, reducing maternal CENP-C or disruption of its dimerization domains impairs CENP-A equalization and chromosome segregation. Therefore, maternal CENP-C acts a key epigenetic regulator that resets centromeric symmetry at fertilization to preserve genome integrity.
    Highlights: CENP-A asymmetry between sperm and oocyte centromeres is a conserved feature from flies to mammals including mice and humans.CENP-A asymmetry between parental centromeres is resolved prior to the first zygotic division via maternally inherited, cytoplasmic CENP-A.Zygotic CENP-A levels in zygotes are regulated in a pronucleus-autonomous manner.CENP-A equalization relies on asymmetric CENP-C recruitment to the paternal pronucleus and requires CENP-C dimerization.
    Key Terms: Centromere; CENP-A; CENP-C; sperm; oocyte; zygote; intergenerational; epigenetics; mouse.
    DOI:  https://doi.org/10.1101/2025.07.23.666394
  10. bioRxiv. 2025 Jul 26. pii: 2025.07.24.666638. [Epub ahead of print]
    Mitotic entry is controlled by the plant-specific phosphatase BSL1 and cyclin-dependent kinase B.
    Frej Tulin, Yalikunjiang Aizezi, Andres V Reyes, Yuji Fujieda, Arthur Grossman, Shou-Ling Xu, Masayuki Onishi, Farhah Assaad, Zhi-Yong Wang.
      Cell cycle regulation is well understood in opisthokonts (fungi and metazoans) but not in plants and Apicomplexa, as some cell cycle regulators are not conserved 1-3 . In opisthokonts, cell cycle progression requires dephosphorylation of cyclin-dependent kinase (CDK) by the CDC25 phosphatase 4 . Plants have no CDC25, and thus their mechanisms of cell cycle regulation remain elusive 1,5,6 . Here, we show that the BSL1 phosphatase dephosphorylates CDKB1 to promote mitotic entry in Chlamydomonas. Mutations of BSL1 or CDKB1 block mitotic entry after DNA replication. BSL1 shows dynamic localization through the cell cycle at the basal bodies, spindle poles, and cleavage furrow. CDKB1 is hyperphosphorylated at T14 and Y15 residues in the bsl1 mutant and in wild-type cells treated with DNA replication inhibitors. BSL1 binds to CDKB1 and dephosphorylates CDKB1 pT14/pY15 in vitro . Phospho-mimicking mutations of T14/Y15 inactivate CDKB1 function, whereas phospho-blocking mutations cause sensitivity to DNA replication inhibitors, which delay cytokinesis in wild-type cells more than cells expressing unphosphorylatable mutant CDKB1. These results indicate that CDKB1 T14/Y15 is phosphorylated to block mitotic entry before DNA replication is complete, and BSL1 dephosphorylates CDKB1 to promote mitosis. Our study demonstrates that BSL1, a phosphatase conserved in plants and Apicomplexa but absent in fungi and animals, is a CDKB1-activating mitosis-promoting factor that has evolved additional signaling functions in receptor kinase pathways in higher plants.
    One-Sentence Summary: BSL1 is a mitosis-promoting phosphatase that activates CDKB1 in plants.
    DOI:  https://doi.org/10.1101/2025.07.24.666638
  11. Mol Cell. 2025 Aug 07. pii: S1097-2765(25)00611-2. [Epub ahead of print]85(15): 2813-2815
    Tethered to survive: Mitotic transcription secures faithful inheritance of extrachromosomal DNA.
    Xue Jin, Roel G W Verhaak.
      In this issue of Molecular Cell, Nichols et al.1 uncover a transcription-dependent tethering mechanism that enables mitotic inheritance of extrachromosomal DNA (ecDNA) in cancer cells, revealing how transcriptionally active ecDNA escapes degradation and drives oncogene persistence through cell division.
    DOI:  https://doi.org/10.1016/j.molcel.2025.07.010
  12. bioRxiv. 2025 Jul 21. pii: 2025.07.17.665461. [Epub ahead of print]
    Interaction of IRS2 with PLK1 protects cells from mitotic stress.
    Ji-Sun Lee, Quyen Thu Bui, Minjeong Jo, Jennifer S Morgan, Isha Nasa, Arminja N Kettenbach, Leslie M Shaw.
      In this study we identify a role for IRS2 in the protection of cells from mitotic stress through its interaction with PLK1. IRS2 is an adaptor protein for the insulin and IGF-1 receptors that mediates their signaling functions. In this capacity, IRS2 is tyrosine phosphorylated to recruit signaling effectors that control cellular outcomes. A role for IRS2 in mitotic regulation has been reported, but the mechanism of IRS2 action in this regulation has not been determined. Here we report that IRS2 interacts with PLK1 in a CDK1-dependent manner, and they co-localize at centrosomes in mitotic cells. In response to mitotic stress, cells that lack IRS2 or express a PLK1-binding deficient mutant exhibit reduced centrosome separation and a shortened mitotic arrest that leads to reduced tumor cell viability. In contrast, cells expressing an IRS2 mutant that is not tyrosine phosphorylated display normal mitotic function. Together, our findings establish a mechanistic connection between IRS2 and mitotic regulation that is distinct from its function as a signaling adaptor protein.
    DOI:  https://doi.org/10.1101/2025.07.17.665461
  13. bioRxiv. 2025 Jul 31. pii: 2025.07.30.665610. [Epub ahead of print]
    Basal Cell-Contact Dynamics Influence Tissue Packing in a Proliferating Mammalian Epithelium.
    Subramanian P Ramanathan, Tanmoy Sarkar, Matej Krajnc, Rosemary Mwithiga, Azize Cerci, Chongbei Zhao, Matthew C Gibson.
      Animal tissue morphology is determined by the shape, position, and proliferative capacity of individual epithelial cells. Nevertheless, it remains incompletely understood how the dynamic shape transformations implicit in mitotic proliferation influence tissue packing, particularly at the level of basal cell contacts. Here, we use an in silico vertex model to show that epithelial mitotic rounding necessitates a sequence of dynamic basal contact rearrangements, including basal diminution of the mitotic cell volume, transient multicellular rosette assembly, basal reinsertion of daughter cells, and neighbor reorganization. We then leverage a mammalian intestinal organoid model to confirm nearly identical basal cell-contact dynamics as those predicted in silico . Pharmacological inhibition of mitotic progression reveals that two events-basal diminution of the cell body and daughter cell reinsertion-independently drive distinct contact rearrangements. Together, our results uncover a previously underappreciated topological role for basal mitotic cell dynamics in shaping epithelial packing and morphogenesis.
    DOI:  https://doi.org/10.1101/2025.07.30.665610
  14. Nat Commun. 2025 Aug 04. 16(1): 7174
    Unequal segregation of mitochondria during asymmetric cell division contributes to cell fate divergence in sister cells in vivo.
    Ioannis Segos, Jens Van Eeckhoven, Simon Berger, Nikhil Mishra, Eric J Lambie, Barbara Conradt.
      The unequal segregation of organelles has been proposed to be an intrinsic mechanism that contributes to cell fate divergence during asymmetric cell division; however, in vivo evidence is sparse. Using super-resolution microscopy, we analysed the segregation of organelles during the division of the neuroblast QL.p in C. elegans larvae. QL.p divides to generate a daughter that survives, QL.pa, and a daughter that dies, QL.pp. We found that mitochondria segregate unequally by density and morphology and that this is dependent on mitochondrial dynamics. Furthermore, we found that mitochondrial density in QL.pp correlates with the time it takes QL.pp to die. We propose that low mitochondrial density in QL.pp promotes the cell death fate and ensures that QL.pp dies in a highly reproducible and timely manner. Our results provide in vivo evidence that the unequal segregation of mitochondria can contribute to cell fate divergence during asymmetric cell division in a developing animal.
    DOI:  https://doi.org/10.1038/s41467-025-62484-5
  15. Nat Commun. 2025 Aug 05. 16(1): 7212
    Arp2/3 and type-I myosins control chromosome mobility and end-resection at double-strand breaks in S. cerevisiae.
    Felix Y Zhou, Marissa Ashton, Yiyang Jiang, Neha Arora, Kevin Clark, Kate B Fitzpatrick, James E Haber.
      Using budding yeast, we show that Arp2/3 actin branching complex has an evolutionarily conserved role in promoting chromosome mobility of double-strand breaks (DSBs). The radius of confinement of a broken chromosome is reduced by inhibiting Arp2/3 or by auxin-induced degron depletion of the nucleation promoting factor Las17WASP or type-1 myosins. Arp2/3 and Las17 are required both to initiate and maintain 5'to 3' resection of DSB ends, whereas depleting Myo3 or Myo5 impairs broken chromosome motion without affecting resection. Conversely, inhibiting Exo1- and Dna2-dependent long-range resection reduces DSB mobility. Inactivating Arp2/3 before DSB induction leads to shortened checkpoint arrest, activating the Tel1ATM/Mre11 (TM) checkpoint. Shortened checkpoint arrest, but not reduced broken chromosome mobility per se, results in reduced interchromosomal homologous recombination. These results suggest that regulating the Arp2/3 complex plays a key role in the processing of DSB ends that is correlated with an increase in DSB mobility and DSB repair.
    DOI:  https://doi.org/10.1038/s41467-025-62377-7
  16. Cell Rep. 2025 Jul 31. pii: S2211-1247(25)00860-5. [Epub ahead of print]44(8): 116089
    Single-cell multiomics reveals the oscillatory dynamics of mRNA metabolism and chromatin accessibility during the cell cycle.
    Maulik K Nariya, David Santiago-Algarra, Olivier Tassy, Marie Cerciat, Tao Ye, Andrea Riba, Nacho Molina.
      The cell cycle is a tightly regulated process that requires precise temporal expression of thousands of cell-cycle-dependent genes. However, the genome-wide dynamics of mRNA metabolism throughout the cell cycle remain uncharacterized. Here, we combined single-cell multiome sequencing, biophysical modeling, and deep learning to quantify rates of mRNA transcription, splicing, nuclear export, and degradation. Our approach revealed that both transcriptional and post-transcriptional processes exhibit distinct oscillatory waves at specific cell cycle phases, with post-transcriptional regulation playing a prominent role in shaping mRNA accumulation. We also observed dynamic changes in chromatin accessibility and transcription factor binding footprints, identifying key regulators underlying the oscillatory dynamics of mRNA. Taken together, the results of our approach uncovered a high-resolution map of RNA metabolism dynamics and chromatin accessibility, offering new insights into the temporal control of gene expression in proliferating cells.
    Keywords:  (post-)transcriptional kinetics; CP: Molecular biology; cell cycle; chromatin accessibility dynamics; gene expression dynamics; mESCs; mRNA metabolism; single-cell multiomics; trajectory inference
    DOI:  https://doi.org/10.1016/j.celrep.2025.116089
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