๐ฐ "Dynamic optimization of extrachromosomal DNA copy number drives tumour evolution"
https://www.biorxiv.org/content/10.64898/2026.03.20.713026v1?rss=1 #CellDivision #Cell
Dynamic optimization of extrachromosomal DNA copy number drives tumour evolution
Extrachromosomal DNA (ecDNA) is common in human cancers and is associated with poor clinical outcomes, yet how ecDNA-driven genetic heterogeneity is translated into functional heterogeneity remains unclear. Using single-cell multiomics sequencing and multiplexed IF-FISH, we show that asymmetric inheritance of ecDNA generates copy number heterogeneity that propagates to gene expression programs, including oncogenic signaling and cellular stress responses. Transgenerational live-cell lineage tracking directly shows that ecDNA heterogeneity arises within only a few cell divisions and modulates daughter cell division timing in a copy number-dependent manner, a property not observed for evenly inherited chromosomal amplicons. We identify an optimal middle ecDNA copy number range that maximizes proliferative fitness at baseline, while drug selection pressure induced by low-dose CHK1 inhibition selects for cells with a new optimal range at low ecDNA copy numbers. These low ecDNA copy number cells pre-exist in the population and can be generated de novo, driving copy number shifts promoting drug resistance. In vivo experiments further demonstrate that shifts toward ecDNA copy numbers that are optimal under the tumour microenvironment enhance tumourigenicity. Together, these findings establish ecDNA copy number plasticity as a central driver of tumour evolution.
### Competing Interest Statement
P.S.M. is a co-founder of Boundless Bio and S1 Oncology. He has equity in both companies and consults, for which he is compensated. H.Y.C. is a co-founder of Accent Therapeutics, Boundless Bio, Cartography Biosciences, and Orbital Therapeutics and was an advisor to 10x Genomics, Arsenal Biosciences, Chroma Medicine, and Exai Bio until Dec 15, 2024. H.Y.C. is an employee and stockholder of Amgen as of Dec. 16, 2024.
bioRxiv๐ฐ "Transertion provides evidence for coupling of transcription and translation in Bacillus subtilis"
https://www.biorxiv.org/content/10.64898/2026.03.21.712414v1?rss=1 #CellDivision #Cell
Transertion provides evidence for coupling of transcription and translation in Bacillus subtilis
In Gram-negative bacteria, co-translational insertion of membrane proteins into the plasma membrane may be coupled to ongoing transcription, a phenomenon known as transertion. Transertion results in a physical shift of the coding gene from the nucleoid towards the membrane and is one of the determinants of the shape of the nucleoid and placement of cell division in Gram-negative bacteria. In contrast, the existence of functional coupling of transcription and translation in Bacillus subtilis and potentially other Gram-positive bacteria has been questioned, suggesting that transertion may not happen. Here, by imaging vertically oriented B. subtilis cells, we show that the gene of a transmembrane protein changes its localization from inside the nucleoid to the plasma membrane upon induction of its transcription. Localization is restored to the nucleoid when induction of transcription has ceased. The shift of the gene towards the membrane is strictly dependent on transcription, its induction, translation and transmembrane nature of the coded protein. These results suggest that, at least, some principles of cellular regulation based on functional coupling of transcription and translation may be conserved between Gram-positive and Gram-negative bacteria.
### Competing Interest Statement
The authors have declared no competing interest.
Wellcome Trust, 217189/Z/19/Z
BBSRC, BB/T017570/1
bioRxiv๐ฐ "Diatom Endosymbionts have Shrinking but Stable Genomes Despite Low Coding Density"
https://www.biorxiv.org/content/10.64898/2026.03.19.712447v1?rss=1 #CellDivision #Cell
Diatom Endosymbionts have Shrinking but Stable Genomes Despite Low Coding Density
Successful establishment of long-term, obligate endosymbiotic relationships requires integration of hosts and endosymbionts across multiple levels. For example, highly integrated, host-beneficial endosymbionts typically have extremely reduced genomes and metabolisms. However, we do not yet fully understand the specific mechanisms that drive this integration or if there is a specific order in which these changes must occur. To investigate the early stages of endosymbiont genome reduction, we greatly expanded available whole genome data for the nitrogen-fixing endosymbionts (spheroid bodies, SBs) of diatoms in the family Rhopalodiaceae. We used these data to reconstruct SB evolutionary history and to characterize SB core metabolic capacity. We found two key genes missing from all SB genomes, mltA and dnaA , which could provide points of host control over SB cell division. Although most of the SB core genome is experiencing moderately strong purifying selection, we identified 54 genes under positive selection. Eighteen of these are peripheral proteins or involved in cell wall and cell membrane metabolism and could be involved in direct interactions with the host. Unexpectedly, we also found three nif genes under positive selection that are core to the central nitrogen-fixing enzyme. Overall, our results provide early insights into how SBs and their hosts interact, showing that SBs are still in the early stages of endosymbiont genome reduction, but they differ in key ways from current models, including the early loss of all mobile elements.
### Competing Interest Statement
The authors have declared no competing interest.
NSF, 2222944
Montana Institute on Ecosystems, https://ror.org/0591pcw70
bioRxiv๐ฐ "Asymmetry and the cytoskeleton: Mechanisms of asymmetric neural stem cell division in Drosophila melanogaster"
https://doi.org/doi:10.1016/bs.ctdb.2025.11.002https://pubmed.ncbi.nlm.nih.gov/41856738/ #CellDivision #Cytoskeleton #Cell๐ฐ "Multi-omic analyses reveal a differential contribution of chromatin-associated PP1 holoenzymes to mitotic exit and G1 re-establishment"
https://doi.org/doi:10.1016/j.devcel.2026.02.016https://pubmed.ncbi.nlm.nih.gov/41850285/ #CellDivision #Cell๐ฐ "Intermitotic timing and motility patterns in the cell division of the diatom Seminavis robusta"
https://arxiv.org/abs/2603.16984 #CellDivision #Q-Bio.Qm
#Cell
Intermitotic timing and motility patterns in the cell division of the diatom Seminavis robusta
Many diatoms follow a size diminuation - size restoration cycle in their vegetative phase, leading to daughter cells that differ in size. For the diatom Seminavis robusta, we investigated by cell tracking over several generations whether the size difference reflects also in different intermitotic times or in the mobility of the cells. A tracking setup and machine-learning based detection algorithm was developed that revealed no significant difference in intermitotic times, a weak coupling to the day- night cycle, and a higher motility of the hypothecal, smaller daughter cell.
arXiv.org๐ฐ "Greatwall Kinase regulates Acute Myeloid Leukaemia Cell Division through a Non-Canonical Mechanism"
https://www.biorxiv.org/content/10.64898/2026.03.16.712046v1?rss=1 #CellDivision #Cell
Greatwall Kinase regulates Acute Myeloid Leukaemia Cell Division through a Non-Canonical Mechanism
Greatwall kinase regulates mitotic progression by phosphorylating ENSA and ARPP19, thereby inhibiting PP2A-B55. Moreover, Greatwall has been implicated in oncogenesis, particularly in solid tumours, but the mechanisms by which Greatwall regulates the cell cycle in other malignancies remain unclear. Here, we show that Greatwall regulates cytokinesis and cell cycle progression in acute myeloid leukaemia (AML) cells through a pathway distinct from ENSA-PP2A-B55. AML cells require Greatwall expression and activity to proliferate, as revealed by pharmacological and systematic genetic perturbation experiments. Mechanistically, Greatwall inactivation or genetic depletion does not measurably affect the ENSA-PP2A-B55 pathway. Instead, loss of Greatwall function alters cytokinesis, and the phosphorylation of proteins involved in cytoskeletal organisation and cytokinesis, including MARK3, which we identify as a direct Greatwall substrate in AML cells. Together, these findings reveal that the Greatwall kinase signalling network is wired differently in leukemic cells, thus uncovering a novel of cell cycle regulation.
bioRxiv๐ฐ "Boundary effects in biological planar networks: pentagonsdominate Pyropia marginal cells"
https://arxiv.org/abs/2503.18855 #CellDivision #Q-Bio.Ot
#Cell
Boundary effects in biological planar networks: pentagonsdominate Pyropia marginal cells
The topological and geometrical features at the boundary zone of planar polygonal networks remain poorly understood. Based on observations and mathematical proofs, we propose that marginal cells in the thalli of Pyropia haitanensis, a two-dimensional (2D) biological polygonal network, have an average edge number of approximately five. We demonstrate that this number is maintained by specific division patterns. Furthermore, we observe that both marginal cells and inner cells follow the trends predicted by the Lewis law and Aboav-Weaire law, but each cell type requires its own set of correlation parameters to more accurately describe its topological and geometrical features. The boundary effects are also evident in the differences between marginal cells and inner cells in terms of the distributions of interior angles and edge lengths. Similar to inner cells, cell division tends to occur in marginal cells with large sizes and transects a pair of unconnected edges. In particular, this study finds that the division of marginal cells preferentially transects the marginal edge. These specific topological and geometrical features of marginal cells and division patterns may inform the development of modelling algorithms for boundary conditions in biological 2D cellular networks.
arXiv.org