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| Open AccessCell cycle transition from S-phase to G1 in Caulobacter is mediated by ancestral virulence regulators
The bacterium Caulobacter crescentus divides asymmetrically to generate a replicative stalk cell and a quiescent swarmer cell. Fumeaux et al. show that MucR zinc-finger transcription factors, which regulate virulence in other species, also control re-entry into quiescence in Caulobacter.
- Coralie Fumeaux
- , Sunish Kumar Radhakrishnan
- & Patrick H. Viollier
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Cell division and targeted cell cycle arrest opens and stabilizes basement membrane gaps
The mechanisms that open and stabilize basement membrane (BM) gaps are poorly understood. Here the authors combine evolutionary and cell biological studies of nematode uterine–vulval attachment to show that BM gaps are widened by cell division and stabilized in their position by attachment to non-dividing cells.
- David Q. Matus
- , Emily Chang
- & David R. Sherwood
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| Open AccessHomeostatic control of polo-like kinase-1 engenders non-genetic heterogeneity in G2 checkpoint fidelity and timing
Cells exposed to DNA damage delay mitotic entry to allow repair. Liang et al. unexpectedly find that the duration of arrest and the completeness of repair vary from cell to cell, determined by progressively increasing polo-like kinase-1 activity, which must pass a threshold to trigger mitosis.
- Hongqing Liang
- , Alessandro Esposito
- & Ashok R. Venkitaraman
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Microcephaly disease gene Wdr62 regulates mitotic progression of embryonic neural stem cells and brain size
Mutations in WD-repeat-containing protein 62 (Wdr62) are associated with microcephaly, a congenital disorder characterized by reduced brain size. The authors show that Wdr62 deficiency in mouse embryos leads to mitotic arrest of neural progenitors and that Wdr62 genetically interacts with Aurora kinase Ato control mitotic progression of neural progenitors.
- Jian-Fu Chen
- , Ying Zhang
- & Lee Niswander
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Structural basis of PcsB-mediated cell separation in Streptococcus pneumoniae
The peptidoglycan hydrolase PcsB is required for cell wall splitting during cell division in Streptococci. Bartual et al.show that PcsB adopts an autoinhibited dimeric structure, and demonstrate the muralytic activity of the uninhibited catalytic domain.
- Sergio G. Bartual
- , Daniel Straume
- & Juan A. Hermoso
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Translation-independent circadian control of the cell cycle in a unicellular photosynthetic eukaryote
Photosynthetic unicellular eukaryotes undergo cell division more frequently at night. Miyagishima et al.show that circadian control of the cell division cycle in unicellular red algae is mediated by phosphorylation of E2F, and that nocturnal cell division protects these cells from photosynthetic oxidative stress.
- Shin-ya Miyagishima
- , Takayuki Fujiwara
- & Mami Nakamura
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The Escherichia coli Tus–Ter replication fork barrier causes site-specific DNA replication perturbation in yeast
Analysis of DNA replication fork arrest is challenging due to lack of techniques that induce site-specific replication barriers in eukaryotic chromosomes. Here, Larsen et al. create a novel tool to trigger targeted replication fork pausing by engineering the bacterial Tus–Tersystem into the yeast genome.
- Nicolai B. Larsen
- , Ehud Sass
- & Ian D. Hickson
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Non-canonical function of spindle assembly checkpoint proteins after APC activation reduces aneuploidy in mouse oocytes
The spindle assembly checkpoint (SAC) has been viewed as a switch that prevents chromosome segregation until all chromosomes are correctly attached to spindle microtubules. Lane and Jones show that in meiosis I, SAC proteins remain partially active after prometaphase, and prevent aneuploidy by prolonging meiosis.
- Simon I.R. Lane
- & Keith T. Jones
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Dynamic phosphorylation of HP1α regulates mitotic progression in human cells
The chromatin-associated protein HP1α is known to also be involved in kinetochore assembly and sister chromatid cohesion. Chakraborty et al.show that phosphorylation at the hinge region of HP1α is required for the onset of mitosis, and facilitates Sgo1 binding to mitotic centromeres.
- Arindam Chakraborty
- , Kannanganattu V. Prasanth
- & Supriya G. Prasanth
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Tousled-like kinases phosphorylate Asf1 to promote histone supply during DNA replication
DNA replication requires re-establishment of chromatin structure, which involves incorporation of newly synthesized histones. Here, Klimovskaia et al.show that phosphorylation of the histone chaperone Asf1 by Tousled-Like Kinase stimulates its ability to bind histones, thus promoting chromatin assembly.
- Ilnaz M. Klimovskaia
- , Clifford Young
- & Anja Groth
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Phosphorylation of ARPP19 by protein kinase A prevents meiosis resumption in Xenopus oocytes
Xenopus oocytes are arrested in prophase of meiosis I due to high protein kinase A (PKA) activity. Dupré et al.identify the PKA substrate responsible for this arrest as ARPP19, and show that its dephosphorylation at S109 is required for meiotic resumption in response to progesterone.
- Aude Dupré
- , Enrico M. Daldello
- & Olivier Haccard
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The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation
On mitotic exit, the nucleoporin MEL-28 binds to chromatin and seeds the formation of nuclear pore complexes. Here Yokoyama et al.show that upon mitotic entry, MEL-28 re-localizes to microtubules where it functions in assembling the mitotic spindle, revealing roles for MEL-28 throughout the cell cycle.
- Hideki Yokoyama
- , Birgit Koch
- & Oliver J. Gruss
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Article
| Open AccessStructural basis for microtubule recognition by the human kinetochore Ska complex
Kinetochores must interact with both polymerizing (straight) and depolymerizing (curved) microtubules to ensure correct mitotic chromosome segregation. Abad et al. reveal how this flexibility is achieved through structural characterization of the interactions between microtubules and the kinetochore protein Ska1.
- Maria Alba Abad
- , Bethan Medina
- & A. Arockia Jeyaprakash
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Poly(ADP-ribose) binding to Chk1 at stalled replication forks is required for S-phase checkpoint activation
DNA damage at stalled replication forks activates Chk1 kinase and poly(ADP-ribose) (PAR) polymerase 1. Min et al.find that retention of Chk1 to stalled replication forks depends on its direct interaction with PAR, and show that PAR chain length fine-tunes Chk1 and S-phase checkpoint activation.
- WooKee Min
- , Christopher Bruhn
- & Zhao-Qi Wang
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TCTP directly regulates ATM activity to control genome stability and organ development in Drosophila melanogaster
Human TCTP, a highly conserved protein linked to tumorigenesis, has been implicated in the cellular DNA damage response in an ATM kinase-dependent manner. Here, Hong et al. demonstrate in vivo that DrosophiladTCTP controls genome stability by enhancing dATM activity towards its substrate H2Av.
- Sung-Tae Hong
- & Kwang-Wook Choi
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APC/C-Cdh1 coordinates neurogenesis and cortical size during development
The E3 ubiquitin ligase APC/C plays a critical role in cell cycle progression. In this study, Delgado-Esteban et al. show that APC/C bound to the co-factor Cdh1 is necessary for neural progenitor cell maintenance and neuronal differentiation.
- Maria Delgado-Esteban
- , Irene García-Higuera
- & Angeles Almeida
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Stepwise histone modifications are mediated by multiple enzymes that rapidly associate with nascent DNA during replication
Chromatin marks have to be re-established after DNA replication. Here Petruk et al. show that many histone-modifying enzymes are found in close proximity to newly replicated DNA in cells of Drosophilaembryos before the corresponding histone marks are re-established.
- Svetlana Petruk
- , Kathryn L. Black
- & Alexander Mazo
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MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination
Meiotic recombination enables reciprocal exchange of genetic material between paternal and maternal homologous chromosomes. Here Luo et al.show that MEIOB, a novel meiosis-specific factor identified in a proteomics screen, forms complexes with RPA2 and SPATA22, and is required for meiotic recombination.
- Mengcheng Luo
- , Fang Yang
- & P. Jeremy Wang
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| Open AccessBod1 regulates protein phosphatase 2A at mitotic kinetochores
PP2A-B56 regulates the stability of kinetochore-microtubule attachments by dephosphorylating several kinetochore proteins. Porter et al. identify Bod1 as a specific inhibitor of PP2A-B56 phosphatase activity and show that this activity is required for proper chromosome alignment during mitosis.
- Iain M. Porter
- , Katharina Schleicher
- & Jason R. Swedlow
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Functional interplay between Aurora B kinase and Ssu72 phosphatase regulates sister chromatid cohesion
The Ssu72 phosphatase is required to prevent premature separation of sister chromatids during interphase. Kim et al.show that this signal is terminated at early mitosis by Aurora B, which phosphorylates Ssu72 and promotes its ubiquitin-dependent degradation.
- Hyun-Soo Kim
- , Se-Hyuk Kim
- & Chang-Woo Lee
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Condensin I associates with structural and gene regulatory regions in vertebrate chromosomes
Condensins participate in the packaging of chromatin during mitosis. Kim et al. discover that condensin I concentrates in centromeres, telomeres and the promoters of active genes in vertebrates, revealing that condensin distribution is remarkably conserved across phylogeny.
- Ji Hun Kim
- , Tao Zhang
- & Damien F. Hudson
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Single-cell dynamics of the chromosome replication and cell division cycles in mycobacteria
Bacterial cell division requires the coordination of chromosome replication with cell growth and division but how these processes are coordinated in mycobacteria is largely unexplored. Santi et al. use single-cell technologies to describe the cell cycle dynamics of Mycobacterium smegmatisand outline important differences in comparison with other bacterial species.
- Isabella Santi
- , Neeraj Dhar
- & John D. McKinney
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Article
| Open AccessATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy
The protein ATG5 is known to be involved in the formation of autophagosomes. Here, Maskey et al. identify a new role of ATG5 in response to drug-induced DNA damage whereby ATG5 translocates to the nucleus, leading to chromosome misalignment and mitotic catastrophe.
- Dipak Maskey
- , Shida Yousefi
- & Hans-Uwe Simon
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A spontaneous Cdt1 mutation in 129 mouse strains reveals a regulatory domain restraining replication licensing
Cdt1 is part of a protein complex that regulates the initiation of DNA replication. Here Coulombe et al. identify a PEST-like regulatory domain in the N terminus of Cdt1 that prevents premature initiation of DNA synthesis during the cell cycle.
- Philippe Coulombe
- , Damien Grégoire
- & Marcel Méchali
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Regulation of the DNA damage response on male meiotic sex chromosomes
The XY body is a structure required for silencing of sex chromosomes, which is enriched in DNA damage response proteins during meiosis in male germ cells. Here, the authors identify differences between the regulation of the DNA damage response at the XY body and in somatic cells.
- Lin-Yu Lu
- , Yi Xiong
- & Xiaochun Yu
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Kindlin-1 regulates mitotic spindle formation by interacting with integrins and Plk-1
Kindlin-1 regulates integrin activation at cell adhesions. Here Patel et al.report that Kindlin-1 also localizes to centrosomes where it controls the formation of mitotic spindles in a manner that requires integrin activation and Kindlin-1 phosphorylation by the mitotic kinase Plk-1.
- Hitesh Patel
- , Judith Zich
- & Valerie G. Brunton
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| Open AccessMechanism of microtubule array expansion in the cytokinetic phragmoplast
Plant cell division is driven by the expansion of the phragmoplast, a characteristic structure that forms in the middle of the plant cell during cytokinesis. Murata et al. use genetic and cell imaging approaches to clarify the microtubule behaviour that leads to phragmoplast expansion.
- Takashi Murata
- , Toshio Sano
- & Mitsuyasu Hasebe
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| Open AccessFork sensing and strand switching control antagonistic activities of RecQ helicases
RecQ helicases are enzymes that play a central role in maintaining genome stability in the DNA repair cascade. Klaue et al. show that RecQ2 and RecQ3 from Arabidopsis thalianaprocess DNA by, respectively, unwinding and rewinding forked DNA substrates, using a frequent strand switching mechanism.
- Daniel Klaue
- , Daniela Kobbe
- & Ralf Seidel
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| Open AccessAurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis
Geminin blocks the inappropriate assembly of pre-replication complexes on DNA, and this activity is inhibited in G1 by its proteasomal degradation. Tsunematsu et al.demonstrate that geminin is stabilized during mitosis due to its phosphorylation by the mitotic kinase Aurora-A.
- Takaaki Tsunematsu
- , Yoshihiro Takihara
- & Yasusei Kudo
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| Open AccessPI 3-kinase-dependent phosphorylation of Plk1–Ser99 promotes association with 14-3-3γ and is required for metaphase–anaphase transition
Polo-like kinase 1 (Plk1) controls the transition between metaphase and anaphase during mitosis. Kasahara et al.show that Plk1 activity is regulated by phosphatidylinositide 3-kinase signalling through phosphorylation at a previously uncharacterized site.
- Kousuke Kasahara
- , Hidemasa Goto
- & Masaki Inagaki
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| Open AccessDll1 maintains quiescence of adult neural stem cells and segregates asymmetrically during mitosis
Neural stem cells in the adult brain maintain their pool size while producing new neurons. Kawaguchi et al.show that, during neural stem cell mitosis in the adult mouse subventricular zone, the Notch ligand Dll1 is asymmetrically segregated to one daughter cell, which undergoes differentiation.
- Daichi Kawaguchi
- , Shohei Furutachi
- & Yukiko Gotoh
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Regulation of asymmetric cell division and polarity by Scribble is not required for humoral immunity
B cells are thought to divide asymmetrically to generate distinct lineages required for adaptive immunity. Hawkins et al. find that surprisingly, mice lacking components of a complex required for asymmetric cell division display normal responses to vaccination and viral infection.
- Edwin D. Hawkins
- , Jane Oliaro
- & Sarah M. Russell
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Rewiring of human lung cell lineage and mitotic networks in lung adenocarcinomas
Directly comparing patterns of gene expression in matched normal and cancerous tissues provides a powerful tool to identify drivers of tumour progression. Here the authors discover genes that are recruited into mitotic signalling networks in lung adenocarcinoma.
- Il-Jin Kim
- , David Quigley
- & Allan Balmain
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Mitotic spindle orientation predicts outer radial glial cell generation in human neocortex
Human neocortex expansion is partly due to neuronal production by outer radial glial cells. In the developing human cortex, LaMonica et al. find that horizontal divisions of ventricular radial glial cells produce outer radial glial cells displaying cell-intrinsic regulation of mitosis and spindle orientation.
- Bridget E. LaMonica
- , Jan H. Lui
- & Arnold R. Kriegstein
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A subset of Drosophila Myc sites remain associated with mitotic chromosomes colocalized with insulator proteins
Myc is a transcription factor present at gene promoters that activates expression of genes involved in pluripotency and cancer. Yang et al. report that Myc is also present at enhancers of Drosophilagenes during interphase and colocalizes with insulator proteins in mitosis.
- Jingping Yang
- , Elizabeth Sung
- & Victor G. Corces
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| Open AccessThe bipolar assembly domain of the mitotic motor kinesin-5
During mitosis, kinesin-5 motors are thought to crosslink microtubules in a muscle-like sliding filament mechanism. By combining electron microscopy with other structural tools, the authors reveal how four kinesin-5 polypeptides are organized into bipolar minifilaments.
- Seyda Acar
- , David B. Carlson
- & Jonathan M. Scholey
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The RB family is required for the self-renewal and survival of human embryonic stem cells
While human embryonic stem cells (ESC) hold great therapeutic promise, many aspects of their basic biology remain poorly understood. Conklin et al.show that too much or too little activation of RB family proteins is detrimental to human ESC populations and identify unique cell cycle regulatory networks in these cells.
- Jamie F. Conklin
- , Julie Baker
- & Julien Sage
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| Open AccessDirect visualization of cell division using high-resolution imaging of M-phase of the cell cycle
Current methods for detecting proliferation in live cells cannot distinguish between dividing cells and cells that are progressing through the cell cycle. Here, a method is described that detects anillin in the contractile ring and in the midbody of cells during M-phase, providing a more accurate detection of dividing cells.
- Michael Hesse
- , Alexandra Raulf
- & Bernd K. Fleischmann
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Article
| Open AccessGreatwall kinase and cyclin B-Cdk1 are both critical constituents of M-phase-promoting factor
Cyclin B–Cdk1 is thought to be synonymous with the promoting factor that drives entry into M-phase of the cell cycle. Here, Greatwall kinase is shown to be required for the breakdown of the nuclear envelope and the assembly of the spindle on entry into M-phase, suggesting that it too is a part of the M-phase-promoting factor.
- Masatoshi Hara
- , Yusuke Abe
- & Takeo Kishimoto
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The critical size is set at a single-cell level by growth rate to attain homeostasis and adaptation
It is assumed that budding yeast need to reach a certain size before entering the cell cycle. Here, using imaging and a mathematical model, Ferrezueloet al.show that there is variability in the size of cells entering the cell cycle and this is controlled by growth rate in G1.
- Francisco Ferrezuelo
- , Neus Colomina
- & Martí Aldea
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DNA replication timing and selection shape the landscape of nucleotide variation in cancer genomes
Cancer cells form by somatic mutations and natural selection, but how these factors affect tumorigenesis is not clear. Here, somatic mutations are characterized in human cancer genomes, revealing that DNA replication timing influences the frequency of single-nucleotide variants in different genomic regions.
- Yong H Woo
- & Wen-Hsiung Li
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Article
| Open AccessFcp1-dependent dephosphorylation is required for M-phase-promoting factor inactivation at mitosis exit
Cyclin B-dependent kinase 1, the M-phase-promoting factor, is precisely activated and inactivated to control mitosis. In this study, Fcp1—the RNA polymerase II-carboxy-terminal domain phosphatase—is identified as a phosphatase required to inactivate the M-phase-promoting factor and promote mitosis exit.
- Roberta Visconti
- , Luca Palazzo
- & Domenico Grieco
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RUNX1-induced silencing of non-muscle myosin heavy chain IIB contributes to megakaryocyte polyploidization
Megakaryocytes undergo polyploidization prior to forming platelets but this process is poorly characterised. In this study, non-muscle myosin IIB heavy chain, that localizes to the contractile ring during mitosis, is shown to be silenced prior to polyploidization in a RUNX1-dependent manner.
- Larissa Lordier
- , Dominique Bluteau
- & Yunhua Chang
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Interpolar microtubules are dispensable in fission yeast meiosis II
Interpolar microtubules were thought to be indispensable for eukaryotic cell division. Here, Akera and colleagues demonstrate that the second division of meiosis in yeast can occur in the absence of interpolar microtubules, and identify the forespore membrane as a force producing structure in cell division.
- Takashi Akera
- , Masamitsu Sato
- & Masayuki Yamamoto
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| Open AccessABL1 regulates spindle orientation in adherent cells and mammalian skin
A systematic approach for identifying the genes responsible for the regulation of spindle orientation in mammals has been lacking. Now, Matsumuraet al. perform a kinase-targeting RNAi screen and identify ABL1, which through the direct phosphorylation of NuMa, is a novel regulator of spindle orientation.
- Shigeru Matsumura
- , Mayumi Hamasaki
- & Fumiko Toyoshima
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The ubiquitin ligase HACE1 regulates Golgi membrane dynamics during the cell cycle
The Golgi membrane is fragmented during mitosis and is subsequently fused following cell division and this process is known to be controlled by ubiquitination. In this study, the ubiquitin ligase HACE1 is shown to be targeted to the Golgi membrane and is required for fusion after the completion of mitosis.
- Danming Tang
- , Yi Xiang
- & Yanzhuang Wang
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| Open AccessA shift of the TOR adaptor from Rictor towards Raptor by semaphorin in C. elegans
What controls the binding partner selection of the target of rapamycin protein, TOR, is unknown. Using theCaenorhabditis elegans tail as a model, Nukazuka et al. determine that signals of semaphorin through plexin control the binding partner selection of TOR and are required for the correct organization of rays in the tail.
- Akira Nukazuka
- , Shusaku Tamaki
- & Shin Takagi
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p53 and p16INK4A independent induction of senescence by chromatin-dependent alteration of S-phase progression
Cellular senescence is characterized by the cessation of cell growth and the expression of the p16 protein. In this study, inhibition or loss of p300, a histone acetyltransferase, is shown to result in senescence that occurs independently of p16 and is associated with histone hypoacetylation and altered replication timing.
- Alexandre Prieur
- , Emilie Besnard
- & Jean-Marc Lemaitre
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Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome
Mutations in the DNA helicaseBLM cause Bloom syndrome, which is characterized by slow replication fork progression and genetic instability. Here, cells lacking BLMare shown to have a defect in cytidine deaminase, which alters the pyrimidine pool and results in replication fork progression with altered velocity.
- Pauline Chabosseau
- , Géraldine Buhagiar-Labarchède
- & Mounira Amor-Guéret