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Condensin dysfunction is a reproductive isolating barrier in mice
Species divergence in condensin regulation and centromere organization between the mice Mus musculus domesticus and Mus spretus drives chromosome decondensation and mis-segregation in their F1 hybrid oocytes, reducing female fertility.
- Warif El Yakoubi
- & Takashi Akera
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RNA polymerase II associates with active genes during DNA replication
Protein complexes containing RNA polymerase II and immature RNA are associated with active genes immediately after replication, suggesting that transmission of active transcriptional states to daughter cells may not require any additional epigenetic bookmarks.
- Tyler K. Fenstermaker
- , Svetlana Petruk
- & Alexander Mazo
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| Open Access
Loss of CDK4/6 activity in S/G2 phase leads to cell cycle reversal
We uncover the mechanism underlying the restriction point phenomenon, suggest a role for cyclin-dependent kinase 4 and 6 activity in S and G2 phases, and explain the behaviour of cells following loss of mitogen signalling.
- James A. Cornwell
- , Adrijana Crncec
- & Steven D. Cappell
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| Open Access
Injury prevents Ras mutant cell expansion in mosaic skin
Following skin injury, wild-type epithelial cells outcompete oncogenic Ras G12V mutant cells owing to differential activation of the EGFR signalling pathway during injury repair.
- Sara Gallini
- , Karl Annusver
- & Valentina Greco
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Mitotic tethering enables inheritance of shattered micronuclear chromosomes
Chromothriptically produced pieces of a micronucleated chromosome are shown to be tethered together in mitosis by a protein complex consisting of MDC1, TOPBP1 and CIP2A, thus enabling their inheritance by a single daughter cell.
- Prasad Trivedi
- , Christopher D. Steele
- & Don W. Cleveland
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| Open Access
Heritable transcriptional defects from aberrations of nuclear architecture
Micronuclei, which are common features of nuclei in cancer cells, can generate heritable sources of transcriptional suppression, a finding that establishes an inherent relationship between chromosomal instability and variation in chromatin state and gene expression.
- Stamatis Papathanasiou
- , Nikos A. Mynhier
- & David Pellman
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| Open Access
Mitotic clustering of pulverized chromosomes from micronuclei
The CIP2A–TOPBP1 complex tethers fragmented chromosomes from micronuclei for asymmetric mitotic inheritance, explaining distinct patterns of chromosome rearrangements in cancers and genomic disorders.
- Yu-Fen Lin
- , Qing Hu
- & Peter Ly
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Alternative CDC20 translational isoforms tune mitotic arrest duration
Human cells modulate the duration of their mitotic arrest through the presence of conserved alternative CDC20 translational isoforms.
- Mary-Jane Tsang
- & Iain M. Cheeseman
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Functional T cells are capable of supernumerary cell division and longevity
Through iterative cycles of viral challenge and rechallenge over ten years, mouse T cells are demonstrated to have essentially infinite potential for population expansion and longevity without malignant transformation or loss of functional competence.
- Andrew G. Soerens
- , Marco Künzli
- & David Masopust
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| Open Access
A mitotic chromatin phase transition prevents perforation by microtubules
Histone deacetylation at the onset of mitosis induces a chromatin-intrinsic phase transition that endows chromosomes with the physical characteristics necessary for their precise movement during cell division.
- Maximilian W. G. Schneider
- , Bryan A. Gibson
- & Daniel W. Gerlich
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| Open Access
Nuclear chromosome locations dictate segregation error frequencies
Using single-cell DNA sequencing after an error-prone mitosis in untransformed, diploid cell lines and organoids, chromosomes are shown to have different segregation error frequencies that result in non-random aneuploidy landscapes.
- Sjoerd J. Klaasen
- , My Anh Truong
- & Geert J. P. L. Kops
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| Open Access
Peptidoglycan maturation controls outer membrane protein assembly
Peptidoglycan stem peptides in the Gram-negative bacterial cell wall regulate the insertion of essential outer membrane proteins, thus representing a potential target for antibiotic design.
- Gideon Mamou
- , Federico Corona
- & Waldemar Vollmer
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| Open Access
Core control principles of the eukaryotic cell cycle
The core cell cycle is largely driven by increasing total CDK activity together with minor differences in the substrate specificity of the CDKs initiating DNA replication and mitosis.
- Souradeep Basu
- , Jessica Greenwood
- & Paul Nurse
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CDC7-independent G1/S transition revealed by targeted protein degradation
In addition to CDC7, the cell cycle kinase CDK1 has a pivotal role in the G1/S transition of cells, a finding that revises our current understanding of cell cycle progression.
- Jan M. Suski
- , Nalin Ratnayeke
- & Piotr Sicinski
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Skin cells undergo asynthetic fission to expand body surfaces in zebrafish
Terminally differentiated superficial epithelial cells continue dividing in the absence of DNA replication to quickly expand epithelial coverage during rapid growth.
- Keat Ying Chan
- , Ching-Cher Sanders Yan
- & Chen-Hui Chen
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| Open Access
CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition
Genome-scale CRISPR–Cas9-based synthetic lethality screens identify PKMYT1 as a potential therapeutic target in tumours with CCNE1 amplification.
- David Gallo
- , Jordan T. F. Young
- & Daniel Durocher
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Cycling cancer persister cells arise from lineages with distinct programs
Lineage tracing by barcoding of individual cells using a lentivirus library shows that cycling and non-cycling drug-tolerant persister cells in cancer arise from different lineages with distinct transcriptional and metabolic programs.
- Yaara Oren
- , Michael Tsabar
- & Aviv Regev
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Structural basis of human separase regulation by securin and CDK1–cyclin B1
Structures of separase in complex with either securin or cyclin B–CDK1 shed light on the regulation of chromosome separation during the cell cycle.
- Jun Yu
- , Pierre Raia
- & Andreas Boland
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Spo11 generates gaps through concerted cuts at sites of topological stress
Meiotic recombination in yeast is not only initiated by single break sites, but also caused by closely spaced Spo11-dependent double-stranded DNA breaks that create chromosomal gaps.
- Silvia Prieler
- , Doris Chen
- & Franz Klein
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Replication stress promotes cell elimination by extrusion
A cell-cycle checkpoint triggers the extrusion of both nematode and mammalian cells experiencing replication stress.
- Vivek K. Dwivedi
- , Carlos Pardo-Pastor
- & H. Robert Horvitz
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CRL4AMBRA1 is a master regulator of D-type cyclins
Biochemical and genetics studies identify CRL4AMBRA1 as the ubiquitin ligase that has a key role in regulating the stability of D-type cyclins during cell-cycle progression.
- Daniele Simoneschi
- , Gergely Rona
- & Michele Pagano
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AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity
AMBRA1-mediated degradation of cyclin D through CRL4–DDB1 regulates cell proliferation and prevents replication stress in neurodevelopment and cancer.
- Emiliano Maiani
- , Giacomo Milletti
- & Francesco Cecconi
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The AMBRA1 E3 ligase adaptor regulates the stability of cyclin D
AMBRA1 is the main regulator of the degradation of D-type cyclins, and loss of AMBRA1 promotes cell proliferation and tumour growth, and reduces the sensitivity of cancer cells to inhibition of CDK4 and CDK6.
- Andrea C. Chaikovsky
- , Chuan Li
- & Julien Sage
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DNA-driven condensation assembles the meiotic DNA break machinery
During meiosis, Mer2 and the Rec114–Mei4 complex form condensates that facilitate the formation of double-strand DNA breaks by recruiting the Spo11 transesterase complex.
- Corentin Claeys Bouuaert
- , Stephen Pu
- & Scott Keeney
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Actin cables and comet tails organize mitochondrial networks in mitosis
During mitosis, complementary actin-based mechanisms ensure equal and random distributions of mitochondria among daughter cells following symmetrical cell division.
- Andrew S. Moore
- , Stephen M. Coscia
- & Erika L. F. Holzbaur
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Centromeres are dismantled by foundational meiotic proteins Spo11 and Rec8
The meiotic proteins Spo11 and Rec8, which ensure meiotic recombination and reductional chromosome segregation, have additional activities that challenge centromere stability by promoting centromeric nucleosome remodelling in both fission yeast and human cells.
- Haitong Hou
- , Eftychia Kyriacou
- & Julia Promisel Cooper
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Spatiotemporal dissection of the cell cycle with single-cell proteogenomics
Spatial and temporal variations among individual human cell proteomes are comprehensively mapped across the cell cycle using proteomic imaging and transcriptomics.
- Diana Mahdessian
- , Anthony J. Cesnik
- & Emma Lundberg
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Whole-genome doubling confers unique genetic vulnerabilities on tumour cells
Cancer cells that have undergone whole-genome doubling are more reliant than their near-diploid counterparts on DNA-replication factors, the spindle-assembly checkpoint and a mitotic kinesin protein, KIF18A.
- Ryan J. Quinton
- , Amanda DiDomizio
- & Neil J. Ganem
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Equilibrium between nascent and parental MCM proteins protects replicating genomes
Mother cells recycle parental MCMs and simultaneously synthesize nascent MCMs, both of which are inherited by daughter cells, in which the former are preferentially used to form active replisomes and the latter adjust the pace of replisome movement to minimize errors during DNA replication.
- Hana Sedlackova
- , Maj-Britt Rask
- & Jiri Lukas
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Conformation of sister chromatids in the replicated human genome
Modified chromosome conformation capture (Hi-C) technology is used to characterize the interactions between sister chromatids, despite their identical DNA sequences.
- Michael Mitter
- , Catherina Gasser
- & Daniel W. Gerlich
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Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer
TRIM37 overexpression promotes centrosome dysfunction that drives genomic instability in breast cancer cell lines containing the recurrent 17q23 amplicon, revealing a vulnerability that can be targeted to eliminate cancer cells.
- Zhong Y. Yeow
- , Bramwell G. Lambrus
- & Andrew J. Holland
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TRIM37 controls cancer-specific vulnerability to PLK4 inhibition
Acentrosomal assembly of the mitotic spindle upon inhibition of the PLK4 protein is shown to depend on the ubiquitin ligase TRIM37, with implications for the use of PLK4 inhibitors to treat neuroblastoma and breast cancer.
- Franz Meitinger
- , Midori Ohta
- & Karen Oegema
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Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly
The surfactant-like protein Ki-67 mediates the clustering of chromosomes during mitotic exit, which displaces large cytoplasmic molecules from the future nuclear space and thus enables the separation of cytoplasmic and nuclear components before the nuclear envelope reforms.
- Sara Cuylen-Haering
- , Mina Petrovic
- & Daniel W. Gerlich
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Keratins are asymmetrically inherited fate determinants in the mammalian embryo
Keratins are determinants of cell fate during mammalian embryogenesis, and are distributed asymmetrically between daughter cells during cell division.
- Hui Yi Grace Lim
- , Yanina D. Alvarez
- & Nicolas Plachta
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Closed mitosis requires local disassembly of the nuclear envelope
In a study performed in Schizosaccharomyces pombe, ‘closed mitosis’ is shown to occur via local disassembly of the nuclear envelope within the narrow bridge connecting segregating daughter nuclei, and a key role is identified for Les1, which restricts nuclear envelope breakdown to the bridge.
- Gautam Dey
- , Siân Culley
- & Buzz Baum
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Regulation of the MLH1–MLH3 endonuclease in meiosis
Reconstitution of the activation of the MLH1–MLH3 endonuclease shows how crossovers are formed during meiosis.
- Elda Cannavo
- , Aurore Sanchez
- & Petr Cejka
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PCNA activates the MutLγ endonuclease to promote meiotic crossing over
A new mechanism explaining how double Holliday junctions are specifically resolved into crossovers during meiosis is shown that resembles the initiation of DNA mismatch repair.
- Dhananjaya S. Kulkarni
- , Shannon N. Owens
- & Neil Hunter
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Convergent genes shape budding yeast pericentromeres
The three-dimensional structure of pericentromeres in budding yeast is defined by convergent genes, which mark pericentromere borders and trap cohesin complexes loaded at centromeres, generating an architecture that allows correct chromosome segregation.
- Flora Paldi
- , Bonnie Alver
- & Adele L. Marston
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A calcineurin–Hoxb13 axis regulates growth mode of mammalian cardiomyocytes
Hoxb13 acts as a cofactor of Meis1 in regulating cardiomyocyte maturation and cell cycle, and knockout of both proteins enables regeneration of postnatal cardiac tissue in a mouse model of heart injury.
- Ngoc Uyen Nhi Nguyen
- , Diana C. Canseco
- & Hesham A. Sadek
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Securin-independent regulation of separase by checkpoint-induced shugoshin–MAD2
Shugoshin and MAD2 regulate separase-mediated chromosome separation during mitosis, in parallel to a previously identified mechanism involving the anaphase inhibitor securin.
- Susanne Hellmuth
- , Laura Gómez-H
- & Olaf Stemmann
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Separase-triggered apoptosis enforces minimal length of mitosis
If early mitosis is too short, separase induces apoptosis by cleaving MCL2 and BCL-XL, thereby eliminating cells that are prone to chromosome missegregation.
- Susanne Hellmuth
- & Olaf Stemmann
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Insights into the assembly and activation of the microtubule nucleator γ-TuRC
The cryo-EM structure of the γ-tubulin ring complex (γ-TuRC) from Xenopus laevis provides insights into the molecular organization of the complex, and shows that actin is a structural component that is functionally relevant to microtubule nucleation.
- Peng Liu
- , Erik Zupa
- & Elmar Schiebel
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Chromatin structure dynamics during the mitosis-to-G1 phase transition
Analysis of the dynamics of chromosome reorganization after exit from mitosis reveals the distinct but mutually influential forces that drive chromatin reconfiguration.
- Haoyue Zhang
- , Daniel J. Emerson
- & Gerd A. Blobel
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Genetic predisposition to mosaic Y chromosome loss in blood
A genome-wide association study of mosaic loss of chromosome Y (LOY) in UK Biobank participants identifies 156 genetic determinants of LOY, showing that LOY is associated with cancer and non-haematological health outcomes.
- Deborah J. Thompson
- , Giulio Genovese
- & John R. B. Perry
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CDK phosphorylation of TRF2 controls t-loop dynamics during the cell cycle
A phospho-switch is identified in the shelterin subunit TRF2 that regulates transient recruitment of the RTEL1 helicase to, and release from, telomeres, and provides a narrow window during which RTEL1 can unwind t-loops to facilitate telomere replication.
- Grzegorz Sarek
- , Panagiotis Kotsantis
- & Simon J. Boulton
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Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome
Cryo-electron microscopy structures of the Saccharomyces cerevisiae inner kinetochore complex provide insights into the interdependencies of constituent subcomplexes and the mechanism of centromeric nucleosome recognition.
- Kaige Yan
- , Jing Yang
- & David Barford
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Asymmetric lysosome inheritance predicts activation of haematopoietic stem cells
The cellular degradative machinery can be asymmetrically inherited upon haematopoietic-stem-cell division, which predicts the future metabolic and translational activation of their daughter cells.
- Dirk Loeffler
- , Arne Wehling
- & Timm Schroeder
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Letter |
Hypo-osmotic-like stress underlies general cellular defects of aneuploidy
A common aneuploidy gene-expression signature is identified in yeast that is suggestive of hypo-osmotic stress, and which leads to cells that exhibit increased plasma-membrane stress and impaired endocytosis.
- Hung-Ji Tsai
- , Anjali R. Nelliat
- & Rong Li
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Letter |
p38γ is essential for cell cycle progression and liver tumorigenesis
The stress-activated kinase p38γ has a role in regulating entry into the cell cycle; in the liver, it can induce cellular proliferation during regeneration and promote the development of hepatocellular carcinoma.
- Antonia Tomás-Loba
- , Elisa Manieri
- & Guadalupe Sabio
Cryo-EM structures of PP2A:B55–FAM122A and PP2A:B55–ARPP19