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| Open AccessA single cyclin–CDK complex is sufficient for both mitotic and meiotic progression in fission yeast
It was recently shown that a single cyclin–CDK complex is sufficient to drive mitosis in fission yeast. Here, the authors show that this complex is also sufficient for meiotic progression, suggesting that specialized complexes are not required for the more intricate transitions of meiosis.
- Pilar Gutiérrez-Escribano
- & Paul Nurse
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Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity
Phosphorylation of insulin receptor substrate (IRS)-1/2 by insulin-like growth factor (IGF)-I receptor tyrosine kinase is essential for IGF signalling. Here, the authors show that monoubiquitination of IRS-2 by the ubiquitin ligase Nedd4 recruits IRS-2 to the cell membrane and increases IRS-2 phosphorylation and IGF signalling.
- Toshiaki Fukushima
- , Hidehito Yoshihara
- & Shin-Ichiro Takahashi
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Rio1 promotes rDNA stability and downregulates RNA polymerase I to ensure rDNA segregation
The protein kinase Rio1 is known to promote 40S ribosome formation in the cytoplasm. Using budding yeast, the authors here show that Rio1 also acts in the nucleus, downregulates rDNA transcription by Pol I, and activates the processing of its transcripts to ensure rDNA stability and segregation.
- Maria G. Iacovella
- , Cristina Golfieri
- & Peter De Wulf
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| Open AccessDissecting meiotic recombination based on tetrad analysis by single-microspore sequencing in maize
The crossovers and gene conversions that occur during meiotic recombination contribute to genome diversity in eukaryotes. Here Li et al. describe a method of isolating individual microspores for whole-genome sequencing, providing new insights into the generation of genome diversity through sexual reproduction.
- Xiang Li
- , Lin Li
- & Jianbing Yan
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| Open AccessAsymmetrically dividing Drosophila neuroblasts utilize two spatially and temporally independent cytokinesis pathways
In asymmetrically dividing cells, both spindle-dependent and spindle-independent cleavage furrow positioning pathways are involved in cytokinesis. Here the authors find that Survivin and the mitotic spindle are required to stabilize the position of the cleavage furrow and to complete cytokinesis in Drosophilaneuroblasts.
- Michaela Roth
- , Chantal Roubinet
- & Clemens Cabernard
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| Open AccessOriented cell division shapes carnivorous pitcher leaves of Sarracenia purpurea
The pitcher-shaped leaf of the carnivorous plant Sarracenia purpurea acts as a pitfall trap to capture small animals. Here, Fukushima et al. analyse pitcher leaf development and propose that this unusual shape evolved from ancestral planar leaves through changes in the orientation of cell division.
- Kenji Fukushima
- , Hironori Fujita
- & Mitsuyasu Hasebe
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TOPBP1 recruits TOP2A to ultra-fine anaphase bridges to aid in their resolution
During chromosome segregation sister chromatids can be entangled, resulting in anaphase bridges that must be resolved. Here, the authors report that topoisomerase IIβ binding protein 1 recruits topoisomerase IIα to centromere-associated ultra-fine anaphase bridges to enable their efficient resolution.
- Ronan Broderick
- , Jadwiga Nieminuszczy
- & Wojciech Niedzwiedz
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Organelles maintain spindle position in plant meiosis
In many plants, male meiosis involves two rounds of chromosome separation without cell division, resulting in two spindles in a single cell. Here Brownfield et al. show that an organelle band acts as a physical barrier between the spindles to ensure accurate chromosome segregation.
- Lynette Brownfield
- , Jun Yi
- & Claudia Köhler
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Article
| Open AccessCenpj/CPAP regulates progenitor divisions and neuronal migration in the cerebral cortex downstream of Ascl1
The proneural factor Ascl1/Mash1 is an important regulator of embryonic neurogenesis. Here the authors identify that the microcephaly protein Cenpj/CPAP is essential for several microtubule-dependent steps in the neurogenic program driven by Ascl1 in the developing cerebral cortex.
- Patricia P. Garcez
- , Javier Diaz-Alonso
- & François Guillemot
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| Open AccessIdentification of FOXM1 as a therapeutic target in B-cell lineage acute lymphoblastic leukaemia
FOXM1, a transcription factor with roles in cell cycle progression, is highly expressed in the majority of solid tumours. Here the authors show that FOXM1 is an ideal therapeutic target in B-cell acute lymphoblastic leukaemia (ALL) due to its dispensability for normal B-cell development.
- Maike Buchner
- , Eugene Park
- & Markus Müschen
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Chromokinesin Kid and kinetochore kinesin CENP-E differentially support chromosome congression without end-on attachment to microtubules
Alignment of chromosomes at the spindle equator involves two kinesin family molecular motors, Kid and CENP-E. Here, Iemura and Tanaka show differential contributions of these motors, whereby Kid promotes partial alignment before end-on microtubule attachment to chromosomes, and CENP-E promotes alignment when microtubules are stabilized.
- Kenji Iemura
- & Kozo Tanaka
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Article
| Open AccessCheckpoints are blind to replication restart and recombination intermediates that result in gross chromosomal rearrangements
Homologous recombination can overcome replication fork inactivation, but this can cause gross chromosomal rearrangements. Here, the authors show that DNA damage and intra-S phase checkpoints are blind to chromosome rearrangement in the first cell cycle, and are only induced in the second cell cycle.
- Saed Mohebi
- , Ken’Ichi Mizuno
- & Johanne M. Murray
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Cerebrospinal fluid-derived Semaphorin3B orients neuroepithelial cell divisions in the apicobasal axis
The spatial orientation of cell divisions is fundamental for tissue architecture and homeostasis but the extracellular cues regulating this process are largely unknown. Here, the authors show that Semaphorin3B released from the floor plate and the nascent choroid plexus controls progenitor division orientation in the developing mouse spinal cord.
- Elise Arbeille
- , Florie Reynaud
- & Valérie Castellani
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| Open AccessReal-time tracking of cell cycle progression during CD8+ effector and memory T-cell differentiation
CD8+ memory T cells appear during infection via a process of selection and differentiation that remains poorly understood. Using a fluorescent indicator of cell cycle progression, Kinjyo et al. show that slow-cycling memory precursors are derived from fast-cycling-activated T cells in influenza-infected mice.
- Ichiko Kinjyo
- , Jim Qin
- & Wolfgang Weninger
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Integration of Hippo signalling and the unfolded protein response to restrain liver overgrowth and tumorigenesis
The Hippo pathway is a major regulator of organ size and growth control. Here Wu et al. provide evidence for a novel link between the Hippo signalling pathway and the unfolded protein response (UPR) in regulating organ growth and tumorigenesis.
- Hongtan Wu
- , Luyao Wei
- & Dawang Zhou
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| Open AccessTemporal and spatial regulation of translation in the mammalian oocyte via the mTOR–eIF4F pathway
Meiotic maturation of oocytes and early development of mammalian embryos is largely dependent on the translation of mRNAs stored in the oocyte. Here the authors uncover a population of mRNA retained in the oocyte nucleus whose translation is spatially and temporally regulated by the mTOR–eIF4F pathway during meiosis.
- Andrej Susor
- , Denisa Jansova
- & Michal Kubelka
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A narrow window of cortical tension guides asymmetric spindle positioning in the mouse oocyte
Asymmetric spindle positioning in female mouse meiosis depends on the assembly of actin networks. Here, Chaigne et al. show by theoretical modelling and artificial manipulation of the oocyte cortex that a narrow stiffness regime is required to correctly position the spindle during meiosis I in the mouse oocyte.
- A. Chaigne
- , C. Campillo
- & M. E. Terret
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FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51
The F-box DNA helicase 1 (FBH1) is implicated in suppression of homologous recombination (HR), but the precise mechanism is unclear. Here, the authors show that FBH1 can ubiquitylate RAD51, a central player in HR, and controls the subcellular localization of RAD51.
- Wai Kit Chu
- , Miranda J. Payne
- & Ian D. Hickson
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| Open AccessCentromeric binding and activity of Protein Phosphatase 4
Many cellular processes, including the cell division cycle, require concerted action of protein kinases and phosphatases. Here Lipinszki et al. present a crystal structure of the Drosophilaphosphoprotein phosphatase 4 subunit, Falafel, in complex with the centromeric protein CENP-C, and reveal a new recognition mode for this phosphatase.
- Zoltan Lipinszki
- , Stephane Lefevre
- & Marcin R. Przewloka
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| Open AccessThe tumour suppressor DLC2 ensures mitotic fidelity by coordinating spindle positioning and cell–cell adhesion
Epithelial cells must position their mitotic spindle correctly to maintain cell–cell adhesion. Here Vitiello et al. show that the tumour suppressor DLC2 and the mitotic kinesin Kif1b coordinate microtubule–actin interactions upstream of mDia3, guiding spindle positioning and mitotic fidelity.
- Elisa Vitiello
- , Jorge G. Ferreira
- & Karl Matter
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Article
| Open AccessSlow unloading leads to DNA-bound β2-sliding clamp accumulation in live Escherichia coli cells
DNA replication is accomplished by the replisome, a multi-protein complex that comprises the sliding clamp. Here, Moolman et al. present quantitative and dynamic measurements of the number of β2-sliding clamps at the single-cell level in live E. colicells to shed light on key aspects of DNA replication.
- M. Charl Moolman
- , Sriram Tiruvadi Krishnan
- & Nynke H. Dekker
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MinCD cell division proteins form alternating copolymeric cytomotive filaments
MinC, MinD and MinE proteins form part of an oscillatory network that ensures bacteria divide precisely at their midpoints. Ghosal et al.show that MinC and MinD can form membrane-binding copolymers, and propose a mechanism by which these copolymers may regulate cytokinetic ring assembly.
- Debnath Ghosal
- , Daniel Trambaiolo
- & Jan Löwe
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The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signalling and silencing
Kinetochores that fail to form bipolar attachments to the mitotic spindle delay chromosome segregation by BubR1 mediated inhibition of Cdc20. Lischetti et al.show that BubR1 recruits Cdc20 to the kinetochore via a domain that mediates both checkpoint activation and silencing.
- Tiziana Lischetti
- , Gang Zhang
- & Jakob Nilsson
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| Open AccessMitotic catenation is monitored and resolved by a PKCε-regulated pathway
Cells are protected from cell division errors by a pathway that detects mitotic catenation. Here, Brownlow et al.show that protein kinase Cε functions in this pathway to drive decatenation, while delaying silencing of the spindle assembly checkpoint to allow time for catenation resolution.
- Nicola Brownlow
- , Tanya Pike
- & Peter J. Parker
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Architecture and dynamic remodelling of the septin cytoskeleton during the cell cycle
In budding yeast, septin filaments adopt an hourglass structure at the bud neck that is remodelled into a double ring. Ong et al.reveal in fine detail the dynamic reorganization of septin filaments within these structures through the cell cycle using platinum-replica electron microscopy.
- Katy Ong
- , Carsten Wloka
- & Erfei Bi
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| Open AccessDynamic SUMO modification regulates mitotic chromosome assembly and cell cycle progression in Caenorhabditis elegans
The ubiquitin-like modifier SUMO is involved in many aspects of the cell cycle, but its dynamics during mitosis are unknown. Here, Pelisch et al.use C. elegans to show that SUMO accumulates on the metaphase plate and is required for proper chromosome alignment, and deconjugation is required to progress through the cell cycle.
- Federico Pelisch
- , Remi Sonneville
- & Ronald T. Hay
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Mus81-Mms4 and Yen1 resolve a novel anaphase bridge formed by noncanonical Holliday junctions
Recombination intermediates must be resolved by mitosis to allow proper chromosome segregation. Here, the authors show that the structure-specific endonucleases Mus81-Msms4 and Yen1 are involved in the resolution of non-canonical Holliday junctions that would otherwise lead to anaphase bridges.
- Jonay García-Luis
- & Félix Machín
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PKM2 phosphorylates MLC2 and regulates cytokinesis of tumour cells
The pyruvate kinase type M2 (PKM2) has a well-established role in cancer due to its functions in regulating glucose metabolism, G1-S transition and mitotic checkpoint. Here the authors identified a novel role for PKM2 in regulating cytokinesis in cancer cells through the phosphorylation of the myosin light chain 2 at the contractile ring.
- Yuhui Jiang
- , Yugang Wang
- & Zhimin Lu
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Article
| Open AccessStructure and function of a spectrin-like regulator of bacterial cytokinesis
EzrA regulates the polymerization of FtsZ, a tubulin-like protein and main component of the Z-ring, which drives cell division in bacteria. Here the authors describe the crystal structure of EzrA and demonstrate that it shares structural and functional properties with eukaryotic spectrins.
- Robert M. Cleverley
- , Jeffrey R. Barrett
- & Richard J. Lewis
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PP2A and Aurora differentially modify Cdc13 to promote telomerase release from telomeres at G2/M phase
Telomere maintenance requires proper termination of telomere replication at G2/M cell cycle stage. Here, Shen et al.show that termination of telomere replication requires PP2A phosphatase and Aurora kinase, which work independently but additively to remove active telomerase from telomeres.
- Zih-Jie Shen
- , Pang-Hung Hsu
- & Shu-Chun Teng
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| Open AccessKinesin-14 and kinesin-5 antagonistically regulate microtubule nucleation by γ-TuRC in yeast and human cells
Mitotic spindle assembly requires strict control of microtubule nucleation by γ-tubulin ring complexes. Olmsted et al. report that the kinesin-like proteins Pkl1 and Cut7 antagonistically regulate nucleation in fission yeast, and show that a Pkl1 peptide blocks spindle assembly in human cancer cells.
- Zachary T. Olmsted
- , Andrew G. Colliver
- & Janet L. Paluh
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FAK transduces extracellular forces that orient the mitotic spindle and control tissue morphogenesis
Orientation of the mitotic spindle is influenced by extracellular forces acting on the cell cortex. Here Petridou et al.identify FAK as a key transducer of mechanical forces in this context and as a result is a key regulator of spindle orientation controlling tissue architecture and morphogenesis.
- Nicoletta I. Petridou
- & Paris A. Skourides
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| Open AccessAlternative meiotic chromatid segregation in the holocentric plant Luzula elegans
Conventionally, meiosis depends on a two-step loss of chromosome cohesion that requires distinction between chromosome arms and sister centromeres. Heckmann et al.show that a plant that lacks a single defined centromere overcomes this problem by inverting the sequence of meiotic segregation events.
- Stefan Heckmann
- , Maja Jankowska
- & Andreas Houben
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| Open AccessChiasmatic and achiasmatic inverted meiosis of plants with holocentric chromosomes
The absence of a defined centromere in organisms with holocentric chromosomes presents particular problems for the control of chromosome segregation during meiosis. Cabral et al.present evidence that two plant species overcome this challenge by inverting the conventional sequence of meiotic divisions.
- Gabriela Cabral
- , André Marques
- & Peter Schlögelhofer
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Endoplasmic reticulum stress sensitizes cells to DNA damage-induced apoptosis through p53-dependent suppression of p21CDKN1A
DNA damage arrests the cell cycle in G1. Mlynarczyk et al.show that endoplasmic reticulum stress impairs DNA damage-induced p21 expression in favour of 14-3-3s-mediated G2 arrest by activating the p53 isoform p53/47, resulting in increased apoptosis in cells exposed to both stressors.
- Coraline Mlynarczyk
- & Robin Fåhraeus
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Stabilization and targeting of INO80 to replication forks by BAP1 during normal DNA synthesis
The INO80 complex is involved in chromatin remodelling during transcription and has been implicated in DNA repair. Here, the authors establish a role for INO80 in normal DNA replication and reveal a mechanism that targets this remodeler to replication forks via BAP1 and H2A ubiquitination.
- Han-Sae Lee
- , Shin-Ai Lee
- & Jongbum Kwon
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Kinetochores require oligomerization of Dam1 complex to maintain microtubule attachments against tension and promote biorientation
The oligomeric Dam1 complex mediates microtubule attachment to kinetochores during mitosis; however, the significance of its oligomeric structure remains unclear. Umbreit et al. show that Dam1 oligomerization is required for microtubules to form attachments that are robust against tension.
- Neil T. Umbreit
- , Matthew P. Miller
- & Trisha N. Davis
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WT1 interacts with MAD2 and regulates mitotic checkpoint function
The transcription factor WT1 can act as either a tumour suppressor or an oncogene by regulating gene expression. Shandilya et al. show that WT1 also directly activates the spindle assembly checkpoint by binding the checkpoint protein MAD2 to delay anaphase and promote chromosomal stability.
- Jayasha Shandilya
- , Eneda Toska
- & Stefan G. E. Roberts
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| Open AccessSize-independent symmetric division in extraordinarily long cells
Known mechanisms that determine symmetric division-plane positioning during cell division are unlikely to operate effectively over very long distances. Pende et al. show that extraordinarily long Gammaproteobacteria divide symmetrically despite reaching 120 microns in length
- Nika Pende
- , Nikolaus Leisch
- & Silvia Bulgheresi
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Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint
During cell division, a single chromosome that lacks attachment to microtubules is sufficient to delay chromosome segregation. Chen and Liu construct a model demonstrating that the transport of regulators along microtubules may explain the remarkable sensitivity and robustness of this checkpoint.
- Jing Chen
- & Jian Liu
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| Open AccessSpatial control of the GEN1 Holliday junction resolvase ensures genome stability
The human Holliday junction resolvase GEN1 functions during anaphase to eliminate recombination intermediates that block proper chromosome segregation. Here, the authors demonstrate that GEN1 activity is regulated independently of its phosphorylation status and relies on its active exclusion from the nucleus.
- Ying Wai Chan
- & Stephen C. West
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The subcortical maternal complex controls symmetric division of mouse zygotes by regulating F-actin dynamics
The mammalian subcortical maternal complex is composed of maternally expressed proteins and required for mouse early embryonic cell division. Here the authors show that the complex functions to control spindle positioning through regulation of the actin cytoskeleton.
- Xing-Jiang Yu
- , Zhaohong Yi
- & Lei Li
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| Open AccessDivision of labour between Myc and G1 cyclins in cell cycle commitment and pace control
The transcription factor E2F is critical for determining cell proliferation. By monitoring E2F activity in single cells throughout the cell cycle, Dong et al.provide evidence that Myc and G1 cyclin/CDKs regulate different aspects of E2F temporal dynamics, resulting in distinct phenotypic outputs.
- Peng Dong
- , Manoj V. Maddali
- & Lingchong You
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Symmetrical and asymmetrical division analysis provides evidence for a hierarchy of prostate epithelial cell lineages
The role of cell division modes of basal and luminal epithelial cells in prostate development and tumorigenesis is unclear. Here, the authors show that while luminal cells contribute to development and tumorigenesis via symmetrical divisions, basal cells do so through asymmetric divisions.
- Jia Wang
- , Helen He Zhu
- & Wei-Qiang Gao
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| Open AccessMyc inhibition is effective against glioma and reveals a role for Myc in proficient mitosis
Myc has been implicated in the development of multiple types of cancer. Here, the authors explore the therapeutic potential and mechanism of action of Myc inhibition in mouse and human models of glioblastoma, an aggressive type of tumour that is often resistant to conventional therapy.
- Daniela Annibali
- , Jonathan R. Whitfield
- & Laura Soucek
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The condensin component NCAPG2 regulates microtubule–kinetochore attachment through recruitment of Polo-like kinase 1 to kinetochores
Polo-like kinase 1 (PLK1) regulates the spindle assembly checkpoint and is recruited to prometaphase kinetochores. Kim et al.show that the condensin subunit NCAPG2 is required for stable interaction of PLK1 with kinetochores and for proper chromosome segregation.
- Jae Hyeong Kim
- , Jaegal Shim
- & Kyung-Tae Kim
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| Open AccessLicensing MLH1 sites for crossover during meiosis
Fertility in polyploid species relies on pairing and recombination occurring only between true homologues rather than the diverged homoeologous chromosomes also present. Here, Martin et al.show that Ph1 stabilises polyploidy in wheat by promoting homologue pairing and preventing crossovers on paired homoeologues during meiosis.
- Azahara C. Martín
- , Peter Shaw
- & Graham Moore
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Pre-anaphase chromosome oscillations are regulated by the antagonistic activities of Cdk1 and PP1 on Kif18A
As chromosomes align during metaphase, they initially oscillate back and forth before settling at the metaphase plate. Häfner et al. show that antagonistic phosphorylation and dephosphorylation of the kinesin Kif18A underlies this behaviour and is required for accurate sister chromatid segregation.
- Julia Häfner
- , Monika I. Mayr
- & Thomas U. Mayer
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Merotelic attachments allow alignment and stabilization of chromatids in meiosis II oocytes
Chromosome mis-segregation is a frequent occurrence in meiosis. Here the authors show that single unpaired chromatids avoid the spindle assembly checkpoint in the second meiotic division as they form bi-directional microtubule–kinetochore attachments, which leads to the completion of meiosis and the establishment of aneuploidy.
- Anna Kouznetsova
- , Abrahan Hernández-Hernández
- & Christer Höög