Featured
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| 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
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Article
| Open AccessRio1 downregulates centromeric RNA levels to promote the timely assembly of structurally fit kinetochores
Kinetochores assemble on centromeres via histone H3 variant CENP-A and low levels of centromere transcripts (cenRNAs). Here the authors show the Rio1 kinase limits cenRNA production by reducing RNAPII accessibility and promotes cenRNA degradation by the 5’− 3’exoribonuclease Rat1.
- Ksenia Smurova
- , Michela Damizia
- & Peter De Wulf
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Article
| Open AccessThe divisome but not the elongasome organizes capsule synthesis in Streptococcus pneumoniae
The bacterial cell envelope consists of multiple layers, the synthesis of which is coordinated through unclear mechanisms. Here, Nakamoto et al. reveal a mechanism linking the synthesis of capsular polysaccharides and cell wall peptidoglycan in pneumococci.
- Rei Nakamoto
- , Sarp Bamyaci
- & Lok-To Sham
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Article
| Open AccessTRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation
cGAS/STING activation is linked to the induction of anti-tumor immune responses. Here the authors report a role for the deubiquitinating enzyme TRABID in regulating mitotic cell division and suppressing anti-tumor immunity, suggesting that TRABID inhibition induces micronuclei and activates cGAS/STING pathway.
- Yu-Hsuan Chen
- , Han-Hsiun Chen
- & Ruey-Hwa Chen
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Article
| Open AccessHDAC9-mediated epithelial cell cycle arrest in G2/M contributes to kidney fibrosis in male mice
Although accumulating evidence indicates that epithelial cell cycle G2/M arrest is involved in kidney fibrosis, the underlying mechanism remains unclear. Here, the authors show that HDAC9 is upregulated in the fibrotic kidney and promotes epithelial cell cycle arrest in G2/M by regulating STAT1.
- Yang Zhang
- , Yujie Yang
- & Fan Yi
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Comment
| Open AccessStructural insights into how augmin augments the mitotic spindle
Cell division critically requires amplification of microtubules (MTs) in the bipolar mitotic spindle. This relies on the filamentous augmin complex that enables MT branching. Studies by Gabel et al., Zupa et al. and Travis et al. describe consistent integrated atomic models of the extraordinarily flexible augmin complex. Their work prompts the question: what is this flexibility really needed for?
- Szymon W. Manka
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Article
| Open AccessIntegrated model of the vertebrate augmin complex
Many microtubules in the mitotic spindle are made through microtubule branching. Here, the authors report a structural model of the augmin complex and insights into its role in microtubule branching.
- Sophie M. Travis
- , Brian P. Mahon
- & Sabine Petry
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Article
| Open AccessDistinct dynein complexes defined by DYNLRB1 and DYNLRB2 regulate mitotic and male meiotic spindle bipolarity
Male meiosis relies on canonical centrosomes for spindle formation, but how this differs from acentrosomal oocyte meiosis is unclear. Here they show that spindle formation in sperm relies on DYNLRB2, similar to the activity of DYNLRB1 in mitotic cells.
- Shuwen He
- , John P. Gillies
- & Hiroki Shibuya
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Article
| Open AccessThe structural flexibility of MAD1 facilitates the assembly of the Mitotic Checkpoint Complex
The formation of the mitotic checkpoint complex requires an intricate spatial coordination amongst the proteins Bub1, Mad1, Cdc20, and Mad2. Chen et al show that a structural flexibility in Mad1 plays an essential role in achieving this coordination.
- Chu Chen
- , Valentina Piano
- & Ajit P. Joglekar
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Article
| Open AccessShort-term molecular consequences of chromosome mis-segregation for genome stability
Chromosomal instability leads to aneuploidy, a state of karyotype imbalance. By inducing controlled chromosome mis-segregation, Santaguida and colleagues show that aneuploidy can also instigate chromosomal instability.
- Lorenza Garribba
- , Giuseppina De Feudis
- & Stefano Santaguida
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Article
| Open AccessNon-canonical functions of SNAIL drive context-specific cancer progression
SNAIL promotes tumour metastasis through inducing epithelial to mesenchymal transition (EMT). Here the authors report that SNAIL bypasses senescence and regulates cell cycle progression to promote pancreatic carcinogenesis and this is independent of EMT induction.
- Mariel C. Paul
- , Christian Schneeweis
- & Dieter Saur
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Article
| Open AccessDNA replication initiation factor RECQ4 possesses a role in antagonizing DNA replication initiation
RECQ4 mutations contribute to multiple developmental diseases and tumorigenesis. Here the authors describe how a highly oncogenic RECQ4 mutation alters the control of DNA synthesis, leading to abnormal DNA content and cell growth.
- Xiaohua Xu
- , Chou-Wei Chang
- & Yilun Liu
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Article
| Open AccessA single-cell transcriptional atlas reveals resident progenitor cell niche functions in TMJ disc development and injury
The transcriptional network in TMJ disc development and injury remains poorly characterized. Here they generate a scRNA-seq atlas of mouse TMJ disc, and identify the resident progenitor population and how its transcriptional reprogramming contributes to disc repair.
- Ruiye Bi
- , Qing Yin
- & Songsong Zhu
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Article
| Open AccessMitotic DNA synthesis in response to replication stress requires the sequential action of DNA polymerases zeta and delta in human cells
DNA replication stress can generate under-replicated DNA regions which is fixed by an atypical form of DNA repair synthesis in mitosis (MiDAS). Here the authors show that translesion and replicative DNA polymerases cooperate via the POLD3 subunit to complete MiDAS in human cells.
- Wei Wu
- , Szymon A. Barwacz
- & Ying Liu
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Article
| Open AccessMaster mitotic kinases regulate viral genome delivery during papillomavirus cell entry
Human papillomavirus (HPV) coopts mitosis for nuclear entry by tethering the viral DNA to mitotic chromosomes, a process facilitated by the viral minor capsid protein L2. Here, Rizzato et al. show that L2 contains conserved phosphorylation motifs within the chromosome-binding region and provide evidence that host master mitotic kinases CDK1 and PLK1 sequentially mediate phosphorylation of L2 at mitosis onset to allow timely tethering of viral DNA to mitotic chromosomes.
- Matteo Rizzato
- , Fuxiang Mao
- & Mario Schelhaas
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Article
| Open AccessPhosphosite Scanning reveals a complex phosphorylation code underlying CDK-dependent activation of Hcm1
Many kinases phosphorylate proteins on multiple sites, however in most cases it is not known which sites are functionally important. Here, the authors describe a high-throughput approach to quantitatively evaluate the contribution of each phosphosite within a multisite phosphorylated domain.
- Michelle M. Conti
- , Rui Li
- & Jennifer A. Benanti
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Article
| Open AccessAnnexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis
Regulation of oriented cell divisions during development is important to position daughter cells and build a structured and functional tissue. Here the authors show that Annexin A1 is a key polarity protein that regulates planar orientation of the cell division axis to guide mammary epithelial morphogenesis.
- Maria Fankhaenel
- , Farahnaz S. Golestan Hashemi
- & Salah Elias
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Article
| Open AccessFunctional crosstalk between the cohesin loader and chromatin remodelers
Chromatin remodelers direct the cohesin loader to nucleosome depleted regions where cohesin accesses chromosomes. Muñoz et al. now show that the cohesin loader in turn is a biochemical activator of a chromatin remodeler, helping to clear nucleosomes
- Sofía Muñoz
- , Andrew Jones
- & Frank Uhlmann
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Article
| Open AccessCENP-F-dependent DRP1 function regulates APC/C activity during oocyte meiosis I
Spindle assembly checkpoint controls anaphase onset and guarantees appropriate chromosome segregation. Here, the authors report that dynamin-related protein 1 is recruited to kinetochores by CENP-F to regulate metaphase-to-anaphase transition by controlling APC/C activity in mouse oocyte meiosis
- Cheng-Jie Zhou
- , Xing-Yue Wang
- & Cheng-Guang Liang
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Article
| Open AccessDOT1L regulates chamber-specific transcriptional networks during cardiogenesis and mediates postnatal cell cycle withdrawal
How and whether histone modifications regulate distinct gene networks remains insufficiently understood. Here Cattaneo et al show that DOT1L catalyzed H3K79me2 regulates fetal chamber-specific gene expression and neonatal cardiomyocyte cell cycle withdrawal to coordinate heart development.
- Paola Cattaneo
- , Michael G. B. Hayes
- & Sylvia M. Evans
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Article
| Open AccessKinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
Mitotic spindle assembly is not fully understood. This work reveals that kinetochores drive the coarsening of a uniform microtubule array into bundles, which promote spindle formation and chromosome segregation fidelity.
- Jurica Matković
- , Subhadip Ghosh
- & Iva M. Tolić
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Article
| Open AccessChromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11
The authors show that polyglutamylation of spindle microtubules is essential for error-free chromosome segregation and is mediated through Tubulin Tyrosine Ligase Like 11 (TTLL11), which is found to be frequently downregulated in cancer.
- Ivan Zadra
- , Senda Jimenez-Delgado
- & Isabelle Vernos
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Article
| Open AccessCell division drives DNA methylation loss in late-replicating domains in primary human cells
DNA methylation loss has been observed in aging tissues and cancers for decades. Researchers from Van Andel Institute have now provided experimental evidence that this process is directly driven by cell division.
- Jamie L. Endicott
- , Paula A. Nolte
- & Peter W. Laird
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Article
| Open AccessPathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy
The SMC5/6 complex is critical for genome stability. Here, the authors identify mutations in SLF2 and SMC5 as cause of Atelís Syndrome characterized by microcephaly, short stature, anemia, segmented chromosomes and mosaic variegated hyperploidy.
- Laura J. Grange
- , John J. Reynolds
- & Grant S. Stewart
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Article
| Open AccessRevealing β-TrCP activity dynamics in live cells with a genetically encoded biosensor
β-TrCP plays an important role in diverse cellular processes such as the cell cycle and inflammation. Here the authors develop a biosensor for β-TrCP activity and use it to investigate β-TrCP dynamics during the cell cycle, and to screen a small-molecule library for β-TrCP activators and inhibitors.
- Debasish Paul
- , Stephen C. Kales
- & Steven D. Cappell
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Article
| Open AccessEngineered helicase replaces thermocycler in DNA amplification while retaining desired PCR characteristics
PCR is an essential method for the amplification and manipulation of nucleic acids, but the requirement for a thermocycler limits access. Here, authors engineer a helicase to replace the heating step of PCR with enzymatic unwinding, allowing the isothermal amplification of fragments up to 6 kb.
- Momčilo Gavrilov
- , Joshua Y. C. Yang
- & Taekjip Ha
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Article
| Open AccessAcute deletion of TET enzymes results in aneuploidy in mouse embryonic stem cells through decreased expression of Khdc3
Inducible disruption of TET dioxygenases in mouse embryonic stem cells results in chromosome mis-segregation and aneuploidies, due to Khdc3 downregulation suggesting a role for TET enzymes and DNA methylation patterns in maintaining genome stability.
- Romain O. Georges
- , Hugo Sepulveda
- & Anjana Rao
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Article
| Open AccessCentral role of Prominin-1 in lipid rafts during liver regeneration
Bahn et al explore the role of the lipid raft protein Prominin-1 in liver regeneration. They show that Prominin-1 promotes hepatocyte proliferation after acute liver injury by interacting with the signal transducer GP130, confining it to lipid rafts and activating IL-6 signaling pathway and eventual activation of STAT3.
- Myeong-Suk Bahn
- , Dong-Min Yu
- & Young-Gyu Ko
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Article
| Open AccessSolving the MCM paradox by visualizing the scaffold of CMG helicase at active replisomes
For several decades the MCM2-7 proteins, the core of the DNA replicative helicase, eluded detection at DNA replication sites. Here, the authors solve this conundrum by gene editing, which enables visualization of replication dynamics in living cells.
- Hana Polasek-Sedlackova
- , Thomas C. R. Miller
- & Jiri Lukas
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Article
| Open AccessEndothelial cell cycle state determines propensity for arterial-venous fate
During blood vessel development, endothelial cells become specified toward arterial or venous fates. Chavkin et al find that distinct endothelial cell cycle states provide windows of opportunity for the molecular induction of arterial or venous fate.
- Nicholas W. Chavkin
- , Gael Genet
- & Karen K. Hirschi
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Article
| Open AccessTubular cell polyploidy protects from lethal acute kidney injury but promotes consequent chronic kidney disease
Acute kidney injury is frequent, often fatal and can leave survivors with chronic kidney disease. Here the authors show that tubular cell polyploidy reduces early fatality sustaining residual function but promotes chronic kidney disease, which can be prevented by blocking YAP1
- Letizia De Chiara
- , Carolina Conte
- & Paola Romagnani
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Article
| Open AccessThe augmin complex architecture reveals structural insights into microtubule branching
The formation of branched microtubule networks in mitotic spindles depends on the augmin complex. Zupa, Würtz et al. elucidate the molecular architecture and conformational plasticity of the augmin complex using integrative structural biology, providing structural insights into microtubule branching.
- Erik Zupa
- , Martin Würtz
- & Stefan Pfeffer
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Article
| Open AccessMolecular architecture of the augmin complex
The eight-subunit augmin complex is required to nucleate branching microtubules and create a robust mitotic spindle during cell division. Here, the authors use cryo-EM, crosslinking mass spectrometry, and computational tools to build a structural model of the human augmin complex.
- Clinton A. Gabel
- , Zhuang Li
- & Leifu Chang
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Article
| Open AccessEvolution of longitudinal division in multicellular bacteria of the Neisseriaceae family
Rod-shaped bacteria typically elongate and divide by transverse fission, but a few species are known to divide longitudinally. Here, the authors use genomic, phylogenetic and microscopy techniques to shed light on the evolution of cell shape, multicellularity and division mode within the family Neisseriaceae.
- Sammy Nyongesa
- , Philipp M. Weber
- & Frédéric J. Veyrier
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Article
| Open AccessEvidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules
Microtubules are built from GDP-tubulin lattices with small GTP caps at their plus-ends. Here, the authors reveal that microtubules that attach to kinetochores in mitosis contain, in addition to the GTP-cap and the GDP-lattices, a dynamic micron-sized mixed-nucleotide zone.
- Cédric Castrogiovanni
- , Alessio V. Inchingolo
- & Patrick Meraldi
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Article
| Open AccessPRC1-mediated epigenetic programming is required to generate the ovarian reserve
In humans, the ovarian reserve is maintained over decades by meiotic arrest of oocytes. Here the authors show that Polycomb Repressive Complex 1 (PRC1)-mediated epigenetic programming is essential for formation of ovarian reserve and thus female reproductive lifespan.
- Mengwen Hu
- , Yu-Han Yeh
- & Satoshi H. Namekawa
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Article
| Open AccessProteomic characterization of the Toxoplasma gondii cytokinesis machinery portrays an expanded hierarchy of its assembly and function
The basal complex is orchestrating Toxoplasma gondii cell division steps. Here, the authors use proximity biotinylation to map the proteome of this contractile ring, identify components acting on its formation, stability and constriction, and reveal bidirectional daughter budding.
- Klemens Engelberg
- , Tyler Bechtel
- & Marc-Jan Gubbels
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Article
| Open AccessA phylogenetically-restricted essential cell cycle progression factor in the human pathogen Candida albicans
Chromosomal instability caused by cell division errors is associated with antifungal drug resistance in fungal pathogens. Here, Jaitly et al. identify several genes involved in chromosomal stability in Candida albicans, including a phylogenetically restricted gene encoding an essential cell-cycle progression factor.
- Priya Jaitly
- , Mélanie Legrand
- & Kaustuv Sanyal
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Article
| Open AccessThe CIP2A-TOPBP1 complex safeguards chromosomal stability during mitosis
In this work, CIP2A is discovered as a TOPBP1-interacting protein that regulates TOPBP1 localization specifically in mitosis. Cells lacking CIP2A display increased radio-sensitivity, micronuclei formation and chromosomal instability.
- Mara De Marco Zompit
- , Mònica Torres Esteban
- & Manuel Stucki
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Article
| Open AccessOncogenic BRAF induces whole-genome doubling through suppression of cytokinesis
Whole-genome doubling (WGD) commonly occurs in many solid tumors. Here the authors use a zebrafish model of melanoma and in vitro models to show that BRAFV600E induces WGD via inhibition of RhoA and cytokinesis failure.
- Revati Darp
- , Marc A. Vittoria
- & Craig J. Ceol
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Article
| Open AccessThe HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors
Long non-coding RNAs (lncRNAs) can contribute to cancers that are driven by Sonic hedgehog (SHH) signaling. Here the authors report that lncRNA HHIP-AS1 stabilises the mRNA of dynein complex 1, thereby, promoting the pro-mitotic effects of SHH-driven tumors.
- Jasmin Bartl
- , Marco Zanini
- & Marc Remke
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Article
| Open AccessInactivation of the Hippo tumor suppressor pathway promotes melanoma
Activating mutations of BRAF alone are inadequate to drive melanoma formation. Here the authors show that activation of Hippo signalling by oncogenic BRAF represents an additional safeguard to limit BRAF-dependent human melanocyte growth and melanoma formation.
- Marc A. Vittoria
- , Nathan Kingston
- & Neil J. Ganem
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Article
| Open AccessG1/S restriction point coordinates phasic gene expression and cell differentiation
Somatic cells display phasic gene expression with compartmentalized gene expression during the cell cycle, while pluripotent cells lack phasic expression. Here, the authors describe a pathway linking microRNA regulation of the G1/S restriction point with phasic gene expression and cell differentiation during mammalian development.
- Brian DeVeale
- , Leqian Liu
- & Robert Blelloch