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| Open AccessVasa nucleates asymmetric translation along the mitotic spindle during unequal cell divisions
Association of mRNA translation with the mitotic spindle is thought to be involved in localized production of cell fate determinants. Here, the authors show Vasa facilitates asymmetric translation, which contributes to differential regulation during sea urchin embryogenesis.
- Ana Fernandez-Nicolas
- , Alicia Uchida
- & Mamiko Yajima
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Article
| Open AccessSpatiotemporal reprogramming of differentiated cells underlies regeneration and neoplasia in the intestinal epithelium
Rapid turnover and regeneration of intestinal epithelium requires distinct intestinal stem cell (ISC) populations. Here the authors show p57 marks quiescent ISCs, and that differentiated cells revert to stem cell state after injury, through dynamic reprogramming characterized by fetal- and metaplastic-like changes.
- Tsunaki Higa
- , Yasutaka Okita
- & Keiichi I. Nakayama
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Article
| Open AccessASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis
The early embryo maintains its structure in the face of large mechanical stresses during morphogenesis. Here they show that ASPP2 acts to preserve epithelial integrity in regions of high apical tension during early development.
- Christophe Royer
- , Elizabeth Sandham
- & Shankar Srinivas
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Article
| Open AccessRecruitment of two Ndc80 complexes via the CENP-T pathway is sufficient for kinetochore functions
The kinetochores contain multiple protein interaction networks. Takenoshita et al. analyzed the complicated networks using the genetic method and revealed that two copies of Ndc80 complexes on CENP-T are sufficient for kinetochore functions.
- Yusuke Takenoshita
- , Masatoshi Hara
- & Tatsuo Fukagawa
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Article
| Open AccessSpatiotemporal expression of regulatory kinases directs the transition from mitosis to cellular morphogenesis in Drosophila
The mechanisms regulating mitosis and differentiation during development are thought to be distinct. Here they show that in Drosophila the mitotic kinase Polo regulates cellular morphogenesis after cell cycle exit.
- Shuo Yang
- , Jennifer McAdow
- & Aaron N. Johnson
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Article
| Open AccessCyclin B/CDK1 and Cyclin A/CDK2 phosphorylate DENR to promote mitotic protein translation and faithful cell division
The cell cycle regulates translation during mitosis by controlling DENR stability. Here, the authors show the non-canonical translation initiation complex DENR·MCTS1 is phosphorylated during mitosis by CDK1 and 2, enabling the translation of genes needed for proper mitotic progression.
- Katharina Clemm von Hohenberg
- , Sandra Müller
- & Aurelio A. Teleman
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Article
| Open AccessThe MuvB complex binds and stabilizes nucleosomes downstream of the transcription start site of cell-cycle dependent genes
The MuvB protein complex regulates genes that are differentially expressed through the cell cycle, yet its precise molecular function has remained unclear. Here the authors reveal MuvB associates with the nucleosome adjacent to the transcription start site of cell-cycle genes and that the tight positioning of this nucleosome correlates with MuvB-dependent gene repression.
- Anushweta Asthana
- , Parameshwaran Ramanan
- & Seth M. Rubin
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Article
| Open AccessNitrogen nutrition contributes to plant fertility by affecting meiosis initiation
Nitrogen deficiency can cause floral abortion during reproductive development of rice. Here the authors show that when nitrogen is limited, rice plants require the ETFβ protein, which is involved in branched chain amino acid catabolism, to promote nitrogen reutilization and support the initiation of meiosis.
- Han Yang
- , Yafei Li
- & Zhukuan Cheng
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Article
| Open AccessSingle-molecule analysis of specificity and multivalency in binding of short linear substrate motifs to the APC/C
The authors used novel single-molecule technology to measure the affinity of interactions between the ubiquitin ligase APC/C and its substrates, providing insights into the control of APC/C substrate destruction during mitosis.
- Nairi Hartooni
- , Jongmin Sung
- & David O. Morgan
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Article
| Open AccessHyphal compartmentalization and sporulation in Streptomyces require the conserved cell division protein SepX
Streptomyces bacteria undergo two modes of cell division: formation of cross-walls in hyphae, leading to multicellular compartments, and septation for release of unicellular spores. Here, Bush et al. identify a protein that is important for both cell division modes in Streptomyces, likely by contributing to stabilization of the divisome.
- Matthew J. Bush
- , Kelley A. Gallagher
- & Susan Schlimpert
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Article
| Open AccessEpoR stimulates rapid cycling and larger red cells during mouse and human erythropoiesis
Maturing erythroblasts become smaller with every cell division. Here, the authors show that Epo stimulation promotes cell division and also generates larger red cells, and that this occurs in mouse and human cells, suggesting that red cell size could be a diagnostic marker for hypoxic stress.
- Daniel Hidalgo
- , Jacob Bejder
- & Merav Socolovsky
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Article
| Open AccessNuMA regulates mitotic spindle assembly, structural dynamics and function via phase separation
Mitotic spindle assembly is required for proper cell division, but many underlying mechanisms remain unclear. Here, the authors show that NuMa undergoes liquid-liquid phase separation, condensing on spindle poles during mitotic entry and enriching critical components to promote spindle assembly.
- Mengjie Sun
- , Mingkang Jia
- & Chuanmao Zhang
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Article
| Open AccessOptogenetic relaxation of actomyosin contractility uncovers mechanistic roles of cortical tension during cytokinesis
The subcellular dynamics of actomyosin contractility is currently hard to study. Here the authors report OptoMYPT, an optogenetic method to induce relaxation of actomyosin contractility by allowing light-dependent recruitment of endogenous protein phosphatase 1c (PP1c) to the plasma membrane.
- Kei Yamamoto
- , Haruko Miura
- & Kazuhiro Aoki
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Article
| Open AccessCounteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation
Chromosome instability frequently occurs due to issues with chromosome-microtubule attachments. Here the authors show that the Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to protect chromosome-microtubule attachments independent of biorientation.
- Xinhong Song
- , Duccio Conti
- & Viji M. Draviam
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Article
| Open AccessThe NUCKS1-SKP2-p21/p27 axis controls S phase entry
Entry into S phase of the cell cycle is regulated positively by mitogens and negatively by DNA damage; however, how balance of these signals is achieved is not well known. Here the authors show that the NUCKS1-SKP2- p21/p27 axis integrates this information, where the NUCKS1 transcription factor affects levels of p21/p27 to readout the mitogen:DNA damage balance and regulate S phase entry decision.
- Samuel Hume
- , Claudia P. Grou
- & Grigory L. Dianov
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Article
| Open AccessA genetically-encoded crosslinker screen identifies SERBP1 as a PKCε substrate influencing translation and cell division
PKCε is known to exert a role in genome protection by directly phosphorylating and switching the specificity of Aurora B. Here the authors identify SERBP1 as a parallel mitotic PKCε substrate controlling translation and ensuring the integrity of chromosome segregation and successful cell division.
- Silvia Martini
- , Khalil Davis
- & Peter J. Parker
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Article
| Open AccessCell-fate transition and determination analysis of mouse male germ cells throughout development
The full-term developmental profile of male germ cells remains undefined. Here, the authors use single-cell sequencing to investigate the transcriptome landscapes of mouse male germ cells throughout development and find several critical regulators for prenatal cell-fate determination.
- Jiexiang Zhao
- , Ping Lu
- & Xiao-Yang Zhao
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Article
| Open AccessMammalian SWI/SNF chromatin remodeler is essential for reductional meiosis in males
The mammalian SWI/SNF nucleosome remodeler is required for spermatogenesis. Here, the authors show that PBAF is essential for meiotic cell division in males and required to activate the expression of critical genes involved in spindle assembly and nuclear division in spermatocytes.
- Debashish U. Menon
- , Oleksandr Kirsanov
- & Terry Magnuson
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Article
| Open AccessCENP-V is required for proper chromosome segregation through interaction with spindle microtubules in mouse oocytes
Chromosome segregation is essential to avoid aneuploidy, yet in mammalian oocytes it progressively fails in an age-dependent manner. Here the authors identify CENP-V as a microtubule binding and bundling protein crucial to faithful oocyte meiosis, and present Cenp-V−/− oocytes as revealing age-dependent weakening of the spindle assembly checkpoint.
- Dalileh Nabi
- , Hauke Drechsler
- & Mariola Chacón
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Article
| Open AccessPDZD-8 and TEX-2 regulate endosomal PI(4,5)P2 homeostasis via lipid transport to promote embryogenesis in C. elegans
Cellular membranes have distinct lipid compositions despite intermixing, and it is unclear why plasma membrane lipids do not accumulate on endosomes. Here, the authors use the C. elegans embryo to identify lipid transfer proteins and phosphatases that are critical for endosomal lipid homeostasis.
- Darshini Jeyasimman
- , Bilge Ercan
- & Yasunori Saheki
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Article
| Open Accessp107 mediated mitochondrial function controls muscle stem cell proliferative fates
The connection between cell cycle, metabolic state and mitochondrial activity is unclear. Here, the authors show that p107 represses mitochondrial transcription and ATP output in response to glycolytic byproducts, causing metabolic control of the cell cycle rate in myogenic progenitors.
- Debasmita Bhattacharya
- , Vicky Shah
- & Anthony Scimè
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Article
| Open AccessSpatiotemporal coordination of the RSF1-PLK1-Aurora B cascade establishes mitotic signaling platforms
During cell division, chromosome alignment is engendered by connection of microtubules to kinetochores, coordinated by Aurora B and PLK1. Here, the authors show that the RSF1-PLK1 axis creates an activating phosphorylation on T236 in the GT motif of Aurora B and this is indispensable for Aurora B activation.
- Ho-Soo Lee
- , Sunwoo Min
- & Hyeseong Cho
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Article
| Open AccessStage-resolved Hi-C analyses reveal meiotic chromosome organizational features influencing homolog alignment
During meiosis, chromosomes undergo dramatic changes in morphology and intranuclear positioning. Here the authors mapped the 3D genome architecture throughout mouse spermatogenesis by Hi-C of sorted cells to reveal the contributions of transcriptional activity and mechanical force in modulating homolog alignment and recombination.
- Wu Zuo
- , Guangming Chen
- & Qian Bian
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Article
| Open AccessWhole chromosome loss and genomic instability in mouse embryos after CRISPR-Cas9 genome editing
A possible undesired outcome of CRISPR-Cas9 germline editing is unwanted karyotype alterations. Here the authors track aberrations through three divisions of embryonic development following Cas9 editing.
- Stamatis Papathanasiou
- , Styliani Markoulaki
- & David Pellman
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Article
| Open AccessThe RAD51 recombinase protects mitotic chromatin in human cells
RAD51 is a well known player of DNA repair and homologous recombination. Here the authors reveal a function for RAD51 in protecting under-replicated DNA in mitotic human cells, promoting mitotic DNA synthesis (MiDAS) and successful chromosome segregation.
- Isabel E. Wassing
- , Emily Graham
- & Fumiko Esashi
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Article
| Open AccessCTCF and transcription influence chromatin structure re-configuration after mitosis
Higher-order chromatin structure is temporarily disrupted during mitosis. Here the authors show that loss of the architectural factor CTCF results in failure to form structural loops and leads to inappropriate cis-regulatory contacts and alterations of compartmental interactions after mitosis. Furthermore, they show global 3D architecture is set up without transcription, but that transcription contributes to proper gene domain formation.
- Haoyue Zhang
- , Jessica Lam
- & Gerd A. Blobel
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Article
| Open AccessThe structure of the bacterial DNA segregation ATPase filament reveals the conformational plasticity of ParA upon DNA binding
ParA is an ATPase involved in the segregation of newly replicated DNA in bacteria. Here, structures of a ParA filament bound to DNA and of ParA in various nucleotide states offer insight into its conformational changes upon DNA binding and filament assembly, including the basis for ParA’s cooperative binding to DNA.
- Alexandra V. Parker
- , Daniel Mann
- & Julien R. C. Bergeron
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Article
| Open AccessRNF168-mediated localization of BARD1 recruits the BRCA1-PALB2 complex to DNA damage
The BRCA1-PALB2-BRCA2-RAD51 (BRCA1-P) complex is well known to play a fundamental role in DNA repair, but how the complex recruitment is regulated is still a matter of interest. Here the authors reveal mechanistic insights into RNF168 activity being responsible for PALB2 recruitment, through BARD1-BRCA1 during homologous recombination repair.
- John J. Krais
- , Yifan Wang
- & Neil Johnson
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Article
| Open AccessAnillin propels myosin-independent constriction of actin rings
Cytokinetic ring constriction during cell division requires actin but curiously is independent of myosin in many organisms. Here, the authors show that anillin, a protein enriched in the contractile ring, is a non-motor actin crosslinker that generates contractile force in lieu of a molecular motor.
- Ondřej Kučera
- , Valerie Siahaan
- & Zdenek Lansky
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Article
| Open AccessDisruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome
Patients with Cornelia de Lange Syndrome (CdLS) often have mutations in cohesin and its regulators; however, the molecular mechanism driving CdLS phenotypes is not well established. Here the authors reveal system skeletal organization genes are downregulated and show that cohesin and its loader Nipbl have altered and decreased genome-wide localization.
- Patricia Garcia
- , Rita Fernandez-Hernandez
- & Ethel Queralt
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Perspective
| Open AccessTowards a synthetic cell cycle
A key feature of living cells is the cell cycle. In this Perspective, the authors explore attempts to recreate this process and what is still required for an integrated synthetic cell cycle.
- Lorenzo Olivi
- , Mareike Berger
- & John van der Oost
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Article
| Open AccessGlucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer
Glucocorticoids (GC) are reported to block cancer cell proliferation, but the mode of action is unclear. Here the authors show that glucocorticoid receptor activation induces cancer cell dormancy in lung cancer by regulating CDKN1C expression through a distal enhancer, and these dormant cells are addicted to IGF-1R signalling pathway.
- Stefan Prekovic
- , Karianne Schuurman
- & Wilbert Zwart
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Article
| Open AccessA prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes
Securin inhibits the protease separase and must be removed before anaphase to ensure timely chromosome segregation. Here, the authors define a mechanism of securin destruction in prometaphase I in mouse oocytes and demonstrate its importance for successful meiotic progression.
- Christopher Thomas
- , Benjamin Wetherall
- & Suzanne Madgwick
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Article
| Open AccessRPA shields inherited DNA lesions for post-mitotic DNA synthesis
Single-stranded DNA during DNA replication and repair in S/G2 needs protection by replication protein A (RPA). Here the authors reveal that RPA also shields inherited single-stranded DNA in G1, representing replication remnants from the previous cell cycle, to allow for post-mitotic DNA synthesis.
- Aleksandra Lezaja
- , Andreas Panagopoulos
- & Matthias Altmeyer
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Article
| Open AccessTuning SAS-6 architecture with monobodies impairs distinct steps of centriole assembly
Centriole biogenesis begins with self-assembly of SAS-6 proteins into 9-fold symmetrical ring polymers, which then stack into a cartwheel that scaffolds organelle formation. Here, the authors develop monobodies against Chlamydomonas reinhardtii SAS-6 and use X-ray crystallography, atomic force microscopy and cryo-electron microscopy to reveal insights into ring assembly and stacking.
- Georgios N. Hatzopoulos
- , Tim Kükenshöner
- & Pierre Gönczy
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Article
| Open AccessThe study of the determinants controlling Arpp19 phosphatase-inhibitory activity reveals an Arpp19/PP2A-B55 feedback loop
Progression of the cell division cycle requires feedback loops including those of phosphorylation and dephosphorylation; however the precise regulation of phosphorylation kinetics of Arpp19, an inhibitor of protein phosphatase 2A, is unclear. Here, the authors report that feedback between phosphorylation states of Ser67 and Ser109 of Arpp19 coordinates Arpp19-dependent inhibition of PP2A-B55 and Cyclin B activation during cell cycle progression.
- Jean Claude Labbé
- , Suzanne Vigneron
- & Thierry Lorca
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Article
| Open AccessThe archaeal protein SepF is essential for cell division in Haloferax volcanii
In most bacteria, cell division depends on tubulin homolog FtsZ and other proteins, such as SepF. Cell division in many archaea also depends on FtsZ. Here, Nußbaum et al. show that a SepF homolog plays important roles in cell division in Haloferax volcanii, a halophilic archaeon that has two FtsZ homologs.
- Phillip Nußbaum
- , Maren Gerstner
- & Sonja-Verena Albers
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Article
| Open AccessClinical CDK4/6 inhibitors induce selective and immediate dissociation of p21 from cyclin D-CDK4 to inhibit CDK2
Clinical CDK4/6 inhibitors are used and tested to treat a variety of cancer types. Here, the authors identify that these drugs work in two ways, a known catalytic role to inhibit kinase activity and a newly discovered noncatalytic role to displace CDK inhibitor p21 from CDK4 but not CDK6 complexes.
- Lindsey R. Pack
- , Leighton H. Daigh
- & Tobias Meyer
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Article
| Open AccessSepF is the FtsZ anchor in archaea, with features of an ancestral cell division system
Most archaea divide by binary fission using an FtsZ-based system that is poorly understood. Here, the authors combine structural, cellular, and evolutionary analyses to show that the SepF protein acts as the FtsZ anchor in the archaeon Methanobrevibacter smithii.
- Nika Pende
- , Adrià Sogues
- & Simonetta Gribaldo
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Article
| Open AccessEstablishment of a fluorescent reporter of RNA-polymerase II activity to identify dormant cells
The identification and characterisation of dormant cells is currently difficult. Here the authors report Optical Stem Cell Activity Reporter (OSCAR) to assess RNA polymerase II activity and identify dormant cell populations in intestinal epithelial cells in vivo.
- Rasmus Freter
- , Paola Falletta
- & Francesco Neri
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Article
| Open AccessMeiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis
The authors add to our knowledge of the transcriptional regulation of the meiotic program in mice spermatocytes, showing ZFP541 regulates meiotic prophase and transition to the division phase by being the target for upstream factors MEIOSIN/STRA8.
- Yuki Horisawa-Takada
- , Chisato Kodera
- & Kei-Ichiro Ishiguro
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Article
| Open AccessHigh proliferation and delamination during skin epidermal stratification
How the developing skin epidermis is transformed from a simple single-layered epithelium to a complex and stratified barrier is still an open question. Here, the authors provide a model based on high proliferation and delamination of the keratinocyte progenitors that support the stratification process.
- Mareike Damen
- , Lisa Wirtz
- & Hisham Bazzi
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Article
| Open AccessInhibition of polar actin assembly by astral microtubules is required for cytokinesis
During cell division, the actin cytoskeletal network at both the equatorial contractile ring and cell cortex are known to play a role, but the regulation of γ-actin during cytokinesis is less well understood. Here, the authors show that recruitment of β-actin to the contractile ring and loss of γ-actin from the cell poles is required for completion of cell division.
- Anan Chen
- , Luisa Ulloa Severino
- & Andrew Wilde
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Article
| Open AccessSmc5/6 functions with Sgs1-Top3-Rmi1 to complete chromosome replication at natural pause sites
Smc5/6, part of the structural maintenance of chromosomes (SMC) family, plays roles in genome structural integrity. Here the authors reveal that Smc5/6 acts jointly with Top3 within the STR complex to mediate DNA replication completion at genomic natural pausing sites (NPSs).
- Sumedha Agashe
- , Chinnu Rose Joseph
- & Dana Branzei
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Article
| Open AccessBora phosphorylation substitutes in trans for T-loop phosphorylation in Aurora A to promote mitotic entry
Tavernier et al. decipher the mechanism by which the intrinsically disordered protein Bora, phosphorylated by Cyclin-Cdk, potentiates AURKA activity towards Polo-like kinase 1. Furthermore, they demonstrate the importance of this mechanism for timely mitotic entry in Xenopus and human cells.
- N. Tavernier
- , Y. Thomas
- & L. Pintard
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Comment
| Open AccessPloidy dynamics increase the risk of liver cancer initiation
Liver cancer typically arises after years of inflammatory insults to hepatocytes. These cells can change their ploidy state during health and disease. Whilst polyploidy may offer some protection, new research shows it may also promote the formation of liver tumours.
- Miryam Müller
- , Stephanie May
- & Thomas G. Bird
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Article
| Open AccessThe M-phase regulatory phosphatase PP2A-B55δ opposes protein kinase A on Arpp19 to initiate meiotic division
Mechanisms triggering meiotic divisions of oocytes remain unclear. Here, the authors report that meiosis resumption relies on the timely phosphorylation of Arpp19 protein at two distinct sites, which depends on two kinases (PKA and Gwl) and a single phosphatase (PP2A-B55δ).
- Tom Lemonnier
- , Enrico Maria Daldello
- & Aude Dupré
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Article
| Open AccessNutrient restriction synergizes with retinoic acid to induce mammalian meiotic initiation in vitro
Retinoic acid is necessary but not sufficient to induce meiosis. Here, the authors use primary mouse undifferentiated spermatogonia culture to show that nutrient restriction, an inducer of yeast meiosis, combined with retinoic acid induces meiotic gene and chromosome programs in mammalian germ cells.
- Xiaoyu Zhang
- , Sumedha Gunewardena
- & Ning Wang
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Article
| Open AccessStabilisation of half MCM ring by Cdt1 during DNA insertion
During pre-Replication Complex, eukaryotic cells load two MCMs into a head-to-head Double Hexamer around duplex DNA (DH). Here the authors preRC assembly assay with purified proteins to reveal insights into S. cerevisiae’s first steps that lead to the DH formation.
- Marina Guerrero-Puigdevall
- , Narcis Fernandez-Fuentes
- & Jordi Frigola