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| Open AccessPhysiological DNA damage promotes functional endoreplication of mammary gland alveolar cells during lactation
Breastfeeding confers lifelong benefits to both mother and child, yet women worldwide experience lactation insufficiency. Here, the authors show that DNA damage occurring in the breast during pregnancy drives the generation of milk-producing cells.
- Rut Molinuevo
- , Julien Menendez
- & Lindsay Hinck
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Article
| Open AccessReciprocal antagonism of PIN1-APC/CCDH1 governs mitotic protein stability and cell cycle entry
Unveiling the regulation of mitotic protein degradation is crucial for cancer therapy. Here, the authors reveal that a reciprocal inhibition of PIN1-APC/CCDH1 controls the cell cycle and mitotic protein degradation, offering a synergistic anti-tumor strategy.
- Shizhong Ke
- , Fabin Dang
- & Kun Ping Lu
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Article
| Open AccessSeeding the meiotic DNA break machinery and initiating recombination on chromosome axes
Meiotic cells deliberately break their DNA to allow chromosomes to swap genetic material. Here, authors reveal genetically separable pathways controlling the seeding and growth of chromosome-bound protein condensates responsible for DNA breaks.
- Ihsan Dereli
- , Vladyslav Telychko
- & Attila Tóth
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Article
| Open AccessOncogenic enhancers prime quiescent metastatic cells to escape NK immune surveillance by eliciting transcriptional memory
Metastasis arises from disseminated tumour cells (DTCs) while the underlying mechanism of DTCs plasticity remains underexplored. Here, the authors show that spatially organized oncogenic enhancers on chromatin sustain the establishment of retinoic acid (RA)-stimulated transcriptional memory through activation of SOX9, supporting the escape of quiescent DTCs from NK-mediated immune surveillance.
- Daniela Michelatti
- , Sven Beyes
- & Alessio Zippo
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Article
| Open AccessA fast-acting lipid checkpoint in G1 prevents mitotic defects
Lipid synthesis increases during the cell cycle to ensure sufficient membrane mass. Here, authors identify a lipid checkpoint in G1 phase that prevents cells from starting the cell cycle if lipid synthesis is low, thereby preventing mitotic defects.
- Marielle S. Köberlin
- , Yilin Fan
- & Tobias Meyer
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| Open AccessRegulation of meiotic telomere dynamics through membrane fluidity promoted by AdipoR2-ELOVL2
Meiosis is a specialized cell division for generating germ cells. The authors show that the lipid composition in the cellular membrane influences meiosis-specific chromosomal dynamics in mouse testis.
- Jingjing Zhang
- , Mario Ruiz
- & Hiroki Shibuya
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Article
| Open AccessSingle-cell division tracing and transcriptomics reveal cell types and differentiation paths in the regenerating lung
This study uses single-cell transcriptomics to examine how lung cells respond to targeted damage. The authors employ genetically modified mouse models and cell sorting to enrich for rare, actively dividing cells, revealing cell types/states and alternative differentiation paths.
- Leila R. Martins
- , Lina Sieverling
- & Claudia Scholl
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Article
| Open AccessCentrosome amplification and aneuploidy driven by the HIV-1-induced Vpr•VprBP•Plk4 complex in CD4+ T cells
People living with HIV-1 are at an increased risk of developing various cancers. Here, the authors suggest that HIV-1-encoded Vpr can promote oncogenesis by forming a ternary complex with VprBP and Plk4 and inducing Plk4-dependent centriole overduplication and aneuploidy.
- Jung-Eun Park
- , Tae-Sung Kim
- & Kyung S. Lee
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Article
| Open AccessCytokinetic abscission requires actin-dependent microtubule severing
Completion of cell division requires severing both the microtubules and the plasma membrane that connects daughter cells. Here, the authors show that branched actin regulates ESCRT localization to promote the microtubule cut, which happens before membrane scission.
- Tamara Advedissian
- , Stéphane Frémont
- & Arnaud Echard
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Article
| Open AccessOncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner
Here the authors report that oncogenic c-Myc induces replication stress via increasing the amount of cohesins bound to chromatin at CTCF sites.
- Silvia Peripolli
- , Leticia Meneguello
- & Robertus A. M. de Bruin
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Article
| Open AccessThe Eyes Absent family members EYA4 and EYA1 promote PLK1 activation and successful mitosis through tyrosine dephosphorylation
The Eyes Absent proteins (EYA1-4) are a group of tyrosine phosphatases. Here, the authors report a signalling pathway in which EYA4 and EYA1 dephosphorylate Polo-like kinase 1 (PLK1) at pY445 to support PLK1 activation and mitosis.
- Christopher B. Nelson
- , Samuel Rogers
- & Hilda A. Pickett
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Article
| Open AccessUltrastructure of macromolecular assemblies contributing to bacterial spore resistance revealed by in situ cryo-electron tomography
Bacterial endospores are among the most resilient forms of life. Here, authors reveal ultrastructural details of the spore chromosome and the multiprotein, multilayered extracellular coat, shedding light on mechanisms contributing to spore resistance.
- Elda Bauda
- , Benoit Gallet
- & Cecile Morlot
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Article
| Open AccessHeterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage
Hepatocytes regenerate the liver after injury, however, the tissue repair mechanisms have been little explored. Here, the authors show that midlobular and pericentral hepatocytes increase their number and size in response to chemical, physical, and viral insults facilitating liver regeneration.
- Inmaculada Ruz-Maldonado
- , John T. Gonzalez
- & Carlos Fernández-Hernando
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Article
| Open AccessRan-GTP assembles a specialized spindle structure for accurate chromosome segregation in medaka early embryos
Mitotic spindle assembles in each blastomere to segregate duplicated chromosomes during cleavage of the fertilized egg. Here, the authors establish functional assays in fish embryos and find that Ran-GTP assembles a microtubule network at the metaphase spindle center that is essential for chromosome segregation.
- Ai Kiyomitsu
- , Toshiya Nishimura
- & Tomomi Kiyomitsu
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Article
| Open AccessRNA polymerase II pausing is essential during spermatogenesis for appropriate gene expression and completion of meiosis
Gene expression dynamics are tightly regulated during spermatogenesis, with disruptions resulting in infertility. Here they identify a critical role for RNA PolII pausing in spermatogenesis and show that loss of the RNA PolII pausing factor NELF causes meiotic arrest.
- Emily G. Kaye
- , Kavyashree Basavaraju
- & Prabhakara P. Reddi
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Article
| Open AccessDeletion of Aurora kinase A prevents the development of polycystic kidney disease in mice
Using different mouse models of Polycystic Kidney Disease, this research demonstrated that deletion of the Aurora Kinase A gene was able to prevent cyst initiation and growth, identifying it as a central regulator of pathogenesis in this condition.
- Ming Shen Tham
- , Denny L. Cottle
- & Ian M. Smyth
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Article
| Open AccessCell cycle arrest induces lipid droplet formation and confers ferroptosis resistance
How cell cycling coordinates with cell survival and death remains unclear. Here, the authors reveal a suppressive effect of cell cycle arrest on ferroptosis and propose a ferroptosis-inducing approach to treat slow-cycling, therapy-resistant cancers.
- Hyemin Lee
- , Amber Horbath
- & Boyi Gan
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Article
| Open AccessAdult stem cell activity in naked mole rats for long-term tissue maintenance
Authors report that long-term intestinal tissue maintenance in naked mole rats is achieved by having an expanded pool of slow-dividing adult stem cells while a higher proportion of differentiated cells confer enhanced function and protection to the intestinal mucosa.
- Shamir Montazid
- , Sheila Bandyopadhyay
- & Shazia Irshad
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Article
| Open AccessContractile ring mechanosensation and its anillin-dependent tuning during early embryogenesis
Contractile ring formation, positioning, and closure is influenced by tissue mechanics, though how this information is transmitted is unclear. Here they show that Anillin is critical for a mechanosensitive pathway that drives cytokinesis and contractile ring closure.
- Christina Rou Hsu
- , Gaganpreet Sangha
- & Kenji Sugioka
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Article
| Open AccessCharacterization of nucleolar SUMO isopeptidases unveils a general p53-independent checkpoint of impaired ribosome biogenesis
Ribosome biogenesis is tightly coordinated with cell-cycle progression. By characterizing the SUMO isopeptidases SENP3/SENP5, Doenig et al. identify a long-sought p53-independent impaired ribosome checkpoint that converges on downregulation of CDK6.
- Judith Dönig
- , Hannah Mende
- & Stefan Müller
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| Open AccessDefining a core configuration for human centromeres during mitosis
The detailed 3D organization of human centromere components is unknown. Here, the authors use super-resolution microscopy to present a working model for a common core centromere structure.
- Ayantika Sen Gupta
- , Chris Seidel
- & Jennifer L. Gerton
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| Open AccessNon-canonical pathway for Rb inactivation and external signaling coordinate cell-cycle entry without CDK4/6 activity
Cyclin-dependent kinases (CDK4/6) play a crucial role in initiating cell growth. Here, Zhang et al. unveil a mechanism that bypasses CDK4/6, shedding light on an alternative pathway of cell-cycle initiation and quiescence maintenance.
- Mimi Zhang
- , Sungsoo Kim
- & Hee Won Yang
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Article
| Open AccessMid-cell migration of the chromosomal terminus is coupled to origin segregation in Escherichia coli
In slow-growing Escherichia coli, the chromosomal terminus is initially located at the new pole and must therefore migrate to midcell during replication to reproduce the same pattern in the daughter cells. Here, Sadhir & Murray use high-throughput time-lapse microscopy to quantify this transition, its timing and its relationship to chromosome segregation, identifying an unexplored connection between the origin of replication locus and the terminus.
- Ismath Sadhir
- & Seán M. Murray
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Article
| Open AccessAn oocyte meiotic midbody cap is required for developmental competence in mice
Midbodies form during cell division and play roles in cell function and fate. Here, the authors show that the meiotic midbody in mouse oocytes has a specialized cap structure required to retain nascent proteins in eggs and for full developmental competence.
- Gyu Ik Jung
- , Daniela Londoño-Vásquez
- & Karen Schindler
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| Open AccessRelease of Histone H3K4-reading transcription factors from chromosomes in mitosis is independent of adjacent H3 phosphorylation
Methyl-phos switches on histones have been shown to regulate reader protein displacement from chromatin. However, in this study the authors find that H3T3ph is not required to remove transcription factors from H3K4me3 in mitosis. This might help to preserve promoter properties during cell division.
- Rebecca J. Harris
- , Maninder Heer
- & Jonathan M. G. Higgins
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Article
| Open AccessHOP1 and HAP2 are conserved components of the meiosis-related machinery required for successful mating in Leishmania
Genetic exchange has been experimentally demonstrated for Leishmania during sand fly development, indicating a meiotic mechanism. Here the authors show that meiosis-related genes HOP1 and HAP2-2 are essential for Leishmania hybridization in vitro and in sand flies and that their deletion in one or both parents hinders mating competence.
- Carolina Moura Costa Catta-Preta
- , Tiago Rodrigues Ferreira
- & David Sacks
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Article
| Open AccessGli1 marks a sentinel muscle stem cell population for muscle regeneration
Adult skeletal muscle regeneration is mainly driven by muscle stem cells (MuSCs), which are highly heterogeneous. Here, the authors found that a population of MuSCs, marked by Gli1 expression, is key contributor to muscle regeneration.
- Jiayin Peng
- , Lili Han
- & Yun Zhao
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Article
| Open AccessProlonging somatic cell proliferation through constitutive hox gene expression in C. elegans
Somatic cells in C. elegans stop dividing after completing their normal lineage at the end of development. Here, Heinze et al. show that constitutive expression of a hox gene prolongs proliferation beyond the restriction imposed by the cell lineage.
- Svenia D. Heinze
- , Simon Berger
- & Alex Hajnal
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Article
| Open AccessFIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination
Assembly and disassembly of RAD51/DMC1 during homologous recombination are tightly regulated. Here, the authors show that the FIGNL1 ATPase limits non-productive assembly of RAD51/DMC1 on single-stranded and double-stranded DNAs during meiosis.
- Masaru Ito
- , Asako Furukohri
- & Akira Shinohara
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Article
| Open AccessSTRA8–RB interaction is required for timely entry of meiosis in mouse female germ cells
Female germ cells initiate meiosis within a limited time period in the fetal ovary. Here the authors show that the interaction between STRA8 and RB ensures precise timing of meiosis initiation and highlight the regulatory mechanisms underlying female-specific meiotic initiation in mice.
- Ryuki Shimada
- , Yuzuru Kato
- & Kei-ichiro Ishiguro
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Article
| Open AccessHierarchical organization and assembly of the archaeal cell sheath from an amyloid-like protein
Cellular cryoET reveals how an amyloid-like protein of the prototypical archaeon, Methanospirillum hungatei, oligomerizes into a ring containing a giant 2700-strand β sheet, and how rings stack into hoops and into the cylindrical sheath of the cell.
- Hui Wang
- , Jiayan Zhang
- & Z. Hong Zhou
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Article
| Open AccessMolecular landscape and functional characterization of centrosome amplification in ovarian cancer
The prevalence of centrosome amplification (CA) and the genomic landscape of chromosomal instability in high-grade serous ovarian carcinoma (HGSOC) remain to be explored. Here the authors suggest CA as a potential driver of tumour evolution and a biomarker for treatment response in HGSOC.
- Carolin M. Sauer
- , James A. Hall
- & James D. Brenton
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Article
| Open AccessMild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1
Mild replication stress leads to premature centriole disengagement while delaying mitotic onset. Here, Dwivedi et al. demonstrate that this results from sub-critical Plk1 kinase activity, enabling centrosome cycling but impeding rapid mitotic entry.
- Devashish Dwivedi
- , Daniela Harry
- & Patrick Meraldi
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Article
| Open AccessBacterial cell-size changes resulting from altering the relative expression of Min proteins
In bacteria such as E. coli, Min proteins ensure proper localization of the septum at the mid-zone of the cell before cell division. Here, the authors study the effects of changes in relative expression of Min proteins on cell size, providing evidence that Min proteins contribute to the regulation of cell size and the timing of septum formation.
- Harsh Vashistha
- , Joanna Jammal-Touma
- & Hanna Salman
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Article
| Open AccessPlasmodium ARK2 and EB1 drive unconventional spindle dynamics, during chromosome segregation in sexual transmission stages
The Aurora kinases orchestrate chromosome segregation and cell division. Zeeshan et al. studied divergent Plasmodium ARK2 and EB1 using live cell imaging, proteomics and functional genetics. These are critical components for atypical spindle dynamics during transmission stages.
- Mohammad Zeeshan
- , Edward Rea
- & Rita Tewari
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Article
| Open AccessCENP-E activation by Aurora A and B controls kinetochore fibrous corona disassembly
It is unknown how the kinetochore fibrous corona is disassembled. Here, the authors reveal that Aurora A and B kinases-mediated phosphorylation activates CENP-E, which is essential to prevent the premature removal of corona proteins by dynein.
- Susana Eibes
- , Girish Rajendraprasad
- & Marin Barisic
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Article
| Open AccessDNAJA2 deficiency activates cGAS-STING pathway via the induction of aberrant mitosis and chromosome instability
Genomic instability can induce an anti-tumour immune response via activation of the cGAS-STING pathway following the formation of micronuclei (MN). Here, the authors identify a role for DNAJA2 in maintenance of chromosomal segregation. Loss of which increased MN formation and cGAS-STING pathway activation, increasing response to immune checkpoint blockade.
- Yaping Huang
- , Changzheng Lu
- & Guo-Min Li
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Article
| Open AccessTRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
The TRAIP E3 ubiquitin ligase is essential for genome integrity, mutations lead to primordial dwarfism in patients. Here, the authors show that TRAIP degradation in S-phase, results in cell arrest due to DNA damage caused by replication-transcription conflicts.
- Shaun Scaramuzza
- , Rebecca M. Jones
- & Agnieszka Gambus
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Article
| Open AccessSCFRMF mediates degradation of the meiosis-specific recombinase DMC1
In eukaryotes the recombinase DMC1 is required for meiotic recombination, but it remains unclear how DMC1 stability is regulated. Here the authors identify a SCF complex which mediates ubiquitination and proteasomal degradation of DMC1.
- Wanyue Xu
- , Yue Yu
- & Yingxiang Wang
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Article
| Open AccessGATA2 mitotic bookmarking is required for definitive haematopoiesis
Most transcription factors detach from chromatin during mitosis, but some are retained and bookmark genomic sites. Here, the authors show that GATA2-mediated mitotic bookmarking is critical for definitive haematopoiesis.
- Rita Silvério-Alves
- , Ilia Kurochkin
- & Carlos-Filipe Pereira
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Article
| Open AccessConformational changes in the essential E. coli septal cell wall synthesis complex suggest an activation mechanism
The divisome is a macromolecular machine composed of more than 30 proteins that controls cell wall constriction during bacterial cell division. Here, the authors provide insights into the structure and dynamics of the divisome core complex using a combination of structure prediction, molecular dynamics simulation, single-molecule imaging, and mutagenesis.
- Brooke M. Britton
- , Remy A. Yovanno
- & Zach Hensel
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Article
| Open AccessThe intensities of canonical senescence biomarkers integrate the duration of cell-cycle withdrawal
Senescence and quiescence are considered different cell states but are hard to distinguish. Here, single-cell imaging followed by immunostaining reveals that the intensities of senescence biomarkers are graded rather than binary, reflecting the duration of cell-cycle withdrawal rather than irreversible cell-cycle arrest.
- Humza M. Ashraf
- , Brianna Fernandez
- & Sabrina L. Spencer
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Article
| Open AccessStructures of a FtsZ single protofilament and a double-helical tube in complex with a monobody
The cryoEM structures of a single protofilament of FtsZ from Klebsiella pneumoniae (KpFtsZ) in a polymerization-preferred conformation are presented and of a double-helical tube of the FtsZ–monobody complex that shows two parallel protofilaments.
- Junso Fujita
- , Hiroshi Amesaka
- & Hiroyoshi Matsumura
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Article
| Open AccessKinetochore component function in C. elegans oocytes revealed by 4D tracking of holocentric chromosomes
The exact function of kinetochore proteins in meiosis remains unclear. Using live imaging of C. elegans oocytes, the authors systematically study the contribution of each kinetochore sub-complex and describe a push-pull mechanism that confers robustness to chromosome segregation.
- Laras Pitayu-Nugroho
- , Mélanie Aubry
- & Julien Dumont
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Article
| Open AccessA PPP-type pseudophosphatase is required for the maintenance of basal complex integrity in Plasmodium falciparum
The authors discover a pseudophosphatase that is an essential component of the basal complex, a contractile ring required for cell division of the malaria parasite. Using a combination of genetics, biochemistry, and cell biology techniques, they demonstrate that the pseudophosphatase, PfPPP8, is critical for integrity and contraction of the basal complex.
- Alexander A. Morano
- , Rachel M. Rudlaff
- & Jeffrey D. Dvorin
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Article
| Open AccessBiomolecular condensate drives polymerization and bundling of the bacterial tubulin FtsZ to regulate cell division
How cell division is regulated with spatiotemporal precision is not fully understood. Here the authors show that a bacterial protein undergoes phase separation through surface-assisted condensation to enrich the tubulin homolog FtsZ in M. xanthus cell division.
- Beatrice Ramm
- , Dominik Schumacher
- & Lotte Søgaard-Andersen
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Article
| Open AccessAcentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract
Microtubules need to be generated during cell division to build mitotic or meiotic spindles. Here, reconstitution experiments and theoretical modeling show that chromosomes alone can trigger branching microtubule nucleation.
- Bernardo Gouveia
- , Sagar U. Setru
- & Sabine Petry
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Article
| Open AccessMultiple ParA/MinD ATPases coordinate the positioning of disparate cargos in a bacterial cell
The ParA/MinD family of ATPases organize diverse genetic- and protein-based cellular cargos in bacteria. Here, Pulianmackal et al. find that over a third of sequenced bacterial genomes encode multiple ParA/MinD ATPases, and show how multiple ParA/MinD ATPases coexist and function to position diverse cargos in the same bacterial cell.
- Lisa T. Pulianmackal
- , Jose Miguel I. Limcaoco
- & Anthony G. Vecchiarelli
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Article
| Open AccessTwo RhoGEF isoforms with distinct localisation control furrow position during asymmetric cell division
This study provides evidence that two RhoGEF isoforms displaying distinct localisation concurrently modulate Rho1 activity to promote robust furrow ingression while preserving cell size asymmetry during neural stem cell division.
- Emilie Montembault
- , Irène Deduyer
- & Anne Royou