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https://www.readbyqxmd.com/read/29773570/hdna2-nuclease-helicase-promotes-centromeric-dna-replication-and-genome-stability
#1
Zhengke Li, Bochao Liu, Weiwei Jin, Xiwei Wu, Mian Zhou, Vincent Wenzhe Liu, Ajay Goel, Zhiyuan Shen, Li Zheng, Binghui Shen
DNA2 is a nuclease/helicase that is involved in Okazaki fragment maturation, replication fork processing, and end resection of DNA double-strand breaks. Similar such helicase activity for resolving secondary structures and structure-specific nuclease activity are needed during DNA replication to process the chromosome-specific higher order repeat units present in the centromeres of human chromosomes. Here, we show that DNA2 binds preferentially to centromeric DNA The nuclease and helicase activities of DNA2 are both essential for resolution of DNA structural obstacles to facilitate DNA replication fork movement...
May 17, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29769405/%C3%AE-synuclein-stimulation-of-monoamine-oxidase-b-and-legumain-protease-mediates-the-pathology-of-parkinson-s-disease
#2
Seong Su Kang, Eun Hee Ahn, Zhentao Zhang, Xia Liu, Fredric P Manfredsson, Ivette M Sandoval, Susov Dhakal, P Michael Iuvone, Xuebing Cao, Keqiang Ye
Dopaminergic neurodegeneration in Parkinson's disease (PD) is associated with abnormal dopamine metabolism by MAO-B (monoamine oxidase-B) and intracellular α-Synuclein (α-Syn) aggregates, called the Lewy body. However, the molecular relationship between α-Syn and MAO-B remains unclear. Here, we show that α-Syn directly binds to MAO-B and stimulates its enzymatic activity, which triggers AEP (asparagine endopeptidase; legumain) activation and subsequent α-Syn cleavage at N103, leading to dopaminergic neurodegeneration...
May 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29769404/dna-activates-the-nse2-mms21-sumo-e3-ligase-in-the-smc5-6-complex
#3
Nathalia Varejão, Eva Ibars, Jara Lascorz, Neus Colomina, Jordi Torres-Rosell, David Reverter
Modification of chromosomal proteins by conjugation to SUMO is a key step to cope with DNA damage and to maintain the integrity of the genome. The recruitment of SUMO E3 ligases to chromatin may represent one layer of control on protein sumoylation. However, we currently do not understand how cells upregulate the activity of E3 ligases on chromatin. Here we show that the Nse2 SUMO E3 in the Smc5/6 complex, a critical player during recombinational DNA repair, is directly stimulated by binding to DNA Activation of sumoylation requires the electrostatic interaction between DNA and a positively charged patch in the ARM domain of Smc5, which acts as a DNA sensor that subsequently promotes a stimulatory activation of the E3 activity in Nse2...
May 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29769403/unmasking-the-skiptic-task-of-tdp-43
#4
Caroline Rouaux, Jose-Luis Gonzalez De Aguilar, Luc Dupuis
No abstract text is available yet for this article.
May 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29769402/gtsf-1-is-required-for-formation-of-a-functional-rna-dependent-rna-polymerase-complex-in-caenorhabditis-elegans
#5
Miguel Vasconcelos Almeida, Sabrina Dietz, Stefan Redl, Emil Karaulanov, Andrea Hildebrandt, Christian Renz, Helle D Ulrich, Julian König, Falk Butter, René F Ketting
Argonaute proteins and their associated small RNAs (sRNAs) are evolutionarily conserved regulators of gene expression. Gametocyte-specific factor 1 (Gtsf1) proteins, characterized by two tandem CHHC zinc fingers and an unstructured C-terminal tail, are conserved in animals and have been shown to interact with Piwi clade Argonautes, thereby assisting their activity. We identified the Caenorhabditis elegans Gtsf1 homolog, named it gtsf-1 and characterized it in the context of the sRNA pathways of C. elegans We report that GTSF-1 is not required for Piwi-mediated gene silencing...
May 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29764982/superman-regulates-floral-whorl-boundaries-through-control-of-auxin-biosynthesis
#6
Yifeng Xu, Nathanaël Prunet, Eng-Seng Gan, Yanbin Wang, Darragh Stewart, Frank Wellmer, Jiangbo Huang, Nobutoshi Yamaguchi, Yoshitaka Tatsumi, Mikiko Kojima, Takatoshi Kiba, Hitoshi Sakakibara, Thomas P Jack, Elliot M Meyerowitz, Toshiro Ito
Proper floral patterning, including the number and position of floral organs in most plant species, is tightly controlled by the precise regulation of the persistence and size of floral meristems (FMs). In Arabidopsis , two known feedback pathways, one composed of WUSCHEL (WUS) and CLAVATA3 (CLV3) and the other composed of AGAMOUS (AG) and WUS, spatially and temporally control floral stem cells, respectively. However, mounting evidence suggests that other factors, including phytohormones, are also involved in floral meristem regulation...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29764981/mice-with-endogenous-tdp-43-mutations-exhibit-gain-of-splicing-function-and-characteristics-of-amyotrophic-lateral-sclerosis
#7
Pietro Fratta, Prasanth Sivakumar, Jack Humphrey, Kitty Lo, Thomas Ricketts, Hugo Oliveira, Jose M Brito-Armas, Bernadett Kalmar, Agnieszka Ule, Yichao Yu, Nicol Birsa, Cristian Bodo, Toby Collins, Alexander E Conicella, Alan Mejia Maza, Alessandro Marrero-Gagliardi, Michelle Stewart, Joffrey Mianne, Silvia Corrochano, Warren Emmett, Gemma Codner, Michael Groves, Ryutaro Fukumura, Yoichi Gondo, Mark Lythgoe, Erwin Pauws, Emma Peskett, Philip Stanier, Lydia Teboul, Martina Hallegger, Andrea Calvo, Adriano Chiò, Adrian M Isaacs, Nicolas L Fawzi, Eric Wang, David E Housman, Francisco Baralle, Linda Greensmith, Emanuele Buratti, Vincent Plagnol, Elizabeth Mc Fisher, Abraham Acevedo-Arozena
TDP-43 (encoded by the gene TARDBP ) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how TARDBP mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous Tardbp to dissect TDP-43 function at physiological levels both in vitro and in vivo Interestingly, we find that mutations within the C-terminal domain of TDP-43 lead to a gain of splicing function. Using two different strains, we are able to separate TDP-43 loss- and gain-of-function effects...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29764980/interplay-of-cell-cell-contacts-and-rhoa-mrtf-a-signaling-regulates-cardiomyocyte-identity
#8
Tatjana Dorn, Jessica Kornherr, Elvira I Parrotta, Dorota Zawada, Harold Ayetey, Gianluca Santamaria, Laura Iop, Elisa Mastantuono, Daniel Sinnecker, Alexander Goedel, Ralf J Dirschinger, Ilaria My, Svenja Laue, Tarik Bozoglu, Christian Baarlink, Tilman Ziegler, Elisabeth Graf, Rabea Hinkel, Giovanni Cuda, Stefan Kääb, Andrew A Grace, Robert Grosse, Christian Kupatt, Thomas Meitinger, Austin G Smith, Karl-Ludwig Laugwitz, Alessandra Moretti
Cell-cell and cell-matrix interactions guide organ development and homeostasis by controlling lineage specification and maintenance, but the underlying molecular principles are largely unknown. Here, we show that in human developing cardiomyocytes cell-cell contacts at the intercalated disk connect to remodeling of the actin cytoskeleton by regulating the RhoA-ROCK signaling to maintain an active MRTF/SRF transcriptional program essential for cardiomyocyte identity. Genetic perturbation of this mechanosensory pathway activates an ectopic fat gene program during cardiomyocyte differentiation, which ultimately primes the cells to switch to the brown/beige adipocyte lineage in response to adipogenesis-inducing signals...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29764979/the-complex-relationship-between-tfeb-transcription-factor-phosphorylation-and-subcellular-localization
#9
REVIEW
Rosa Puertollano, Shawn M Ferguson, James Brugarolas, Andrea Ballabio
The MiT-TFE family of basic helix-loop-helix leucine-zipper transcription factors includes four members: TFEB, TFE3, TFEC, and MITF Originally described as oncogenes, these factors play a major role as regulators of lysosome biogenesis, cellular energy homeostasis, and autophagy. An important mechanism by which these transcription factors are regulated involves their shuttling between the surface of lysosomes, the cytoplasm, and the nucleus. Such dynamic changes in subcellular localization occur in response to nutrient fluctuations and various forms of cell stress and are mediated by changes in the phosphorylation of multiple conserved amino acids...
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29764978/the-hfq-chaperone-helps-the-ribosome-mature
#10
Indra Mani Sharma, Arthur Korman, Sarah A Woodson
No abstract text is available yet for this article.
May 15, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29752423/strong-homeostatic-tcr-signals-induce-formation-of-self-tolerant-virtual-memory-cd8-t-cells
#11
Ales Drobek, Alena Moudra, Daniel Mueller, Martina Huranova, Veronika Horkova, Michaela Pribikova, Robert Ivanek, Susanne Oberle, Dietmar Zehn, Kathy D McCoy, Peter Draber, Ondrej Stepanek
Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8+ T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells...
May 11, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29735571/don-t-go-in-circles-confounding-factors-in-gene-expression-profiling
#12
John Toubia, Vanessa M Conn, Simon J Conn
No abstract text is available yet for this article.
May 7, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29728368/-in-vivo-expansion-of-functionally-integrated-gabaergic-interneurons-by-targeted-increase-in-neural-progenitors
#13
Rachel E Shaw, Benjamin Kottler, Zoe N Ludlow, Edgar Buhl, Dongwook Kim, Sara Morais da Silva, Alina Miedzik, Antoine Coum, James Jl Hodge, Frank Hirth, Rita Sousa-Nunes
A central hypothesis for brain evolution is that it might occur via expansion of progenitor cells and subsequent lineage-dependent formation of neural circuits. Here, we report in vivo amplification and functional integration of lineage-specific circuitry in Drosophila Levels of the cell fate determinant Prospero were attenuated in specific brain lineages within a range that expanded not only progenitors but also neuronal progeny, without tumor formation. Resulting supernumerary neural stem cells underwent normal functional transitions, progressed through the temporal patterning cascade, and generated progeny with molecular signatures matching source lineages...
May 4, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29724755/the-helicobacter-pylori-adhesin-protein-hopq-exploits-the-dimer-interface-of-human-ceacams-to-facilitate-translocation-of-the-oncoprotein-caga
#14
Daniel A Bonsor, Qing Zhao, Barbara Schmidinger, Evelyn Weiss, Jingheng Wang, Daniel Deredge, Robert Beadenkopf, Blaine Dow, Wolfgang Fischer, Dorothy Beckett, Patrick L Wintrode, Rainer Haas, Eric J Sundberg
Helicobacter pylori infects half of the world's population, and strains that encode the cag type IV secretion system for injection of the oncoprotein CagA into host gastric epithelial cells are associated with elevated levels of cancer. CagA translocation into host cells is dependent on interactions between the H. pylori adhesin protein HopQ and human CEACAMs. Here, we present high-resolution structures of several HopQ-CEACAM complexes and CEACAMs in their monomeric and dimeric forms establishing that HopQ uses a coupled folding and binding mechanism to engage the canonical CEACAM dimerization interface for CEACAM recognition...
May 3, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29712715/nmdar-dependent-argonaute-2-phosphorylation-regulates-mirna-activity-and-dendritic-spine-plasticity
#15
Dipen Rajgor, Thomas M Sanderson, Mascia Amici, Graham L Collingridge, Jonathan G Hanley
MicroRNAs (miRNAs) repress translation of target mRNAs by associating with Argonaute (Ago) proteins to form the RNA-induced silencing complex (RISC), underpinning a powerful mechanism for fine-tuning protein expression. Specific miRNAs are required for NMDA receptor (NMDAR)-dependent synaptic plasticity by modulating the translation of proteins involved in dendritic spine morphogenesis or synaptic transmission. However, it is unknown how NMDAR stimulation stimulates RISC activity to rapidly repress translation of synaptic proteins...
April 30, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29669863/continuous-signaling-of-cd79b-and-cd19-is-required-for-the-fitness-of-burkitt-lymphoma-b-cells
#16
Xiaocui He, Kathrin Kläsener, Joseena M Iype, Martin Becker, Palash C Maity, Marco Cavallari, Peter J Nielsen, Jianying Yang, Michael Reth
Expression of the B-cell antigen receptor (BCR) is essential not only for the development but also for the maintenance of mature B cells. Similarly, many B-cell lymphomas, including Burkitt lymphoma (BL), require continuous BCR signaling for their tumor growth. This growth is driven by immunoreceptor tyrosine-based activation motif (ITAM) and PI3 kinase (PI3K) signaling. Here, we employ CRISPR/Cas9 to delete BCR and B-cell co-receptor genes in the human BL cell line Ramos. We find that Ramos B cells require the expression of the BCR signaling component Igβ (CD79b), and the co-receptor CD19, for their fitness and competitive growth in culture...
April 18, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29669862/past-stem-cells-and-finally-in-transit-slc1a3-instructs-skin-niche-coupling
#17
Edwige Roy, Kiarash Khosrotehrani
No abstract text is available yet for this article.
April 18, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29669861/informational-limits-of-biological-organisms
#18
Jussi Taipale
No abstract text is available yet for this article.
April 18, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29669860/thermal-proteome-profiling-of-breast-cancer-cells-reveals-proteasomal-activation-by-cdk4-6-inhibitor-palbociclib
#19
Teemu P Miettinen, Julien Peltier, Anetta Härtlova, Marek Gierliński, Valerie M Jansen, Matthias Trost, Mikael Björklund
Palbociclib is a CDK4/6 inhibitor approved for metastatic estrogen receptor-positive breast cancer. In addition to G1 cell cycle arrest, palbociclib treatment results in cell senescence, a phenotype that is not readily explained by CDK4/6 inhibition. In order to identify a molecular mechanism responsible for palbociclib-induced senescence, we performed thermal proteome profiling of MCF7 breast cancer cells. In addition to affecting known CDK4/6 targets, palbociclib induces a thermal stabilization of the 20S proteasome, despite not directly binding to it...
April 18, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29669859/anti-cancer-therapy-senescence-is-the-new-black
#20
Rodrigo Leite de Oliveira, Rene Bernards
No abstract text is available yet for this article.
April 18, 2018: EMBO Journal
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