Table of Contents
Volume 31, Number 9, 2 May 2012
Have you seen?
- The many functions of cohesin—different rings to rule them all?
- ↵*Correspondence to: peters{at}imp.ac.at
It is well known that somatic and germ cells use different cohesin complexes tomediate sister chromatid cohesion, but why different isoforms of cohesin alsoco‐exist within somatic vertebrate cells has remained a mystery. Two papers in thisissue of The EMBO Journal have begun to address this question by analysingmouse cells lacking SA1, an isoform of a specific cohesin subunit.
There is an Article (May 2012) associated with this Have you seen?.
Two studies generating and characterizing mice that lack the core cohesin subunit SA1reveal its essential roles in telomere replication and gene expression, which cannotbe taken over by cohesin complexes containing the paralog SA2.
- Copyright © 2012 European Molecular Biology Organization
- Lrig1: a new master regulator of epithelial stem cells
- 1 École Polytechnique Fédérale de Lausanne (EPFL), ISREC (Swiss Institute for Experimental Cancer Research) and National Center of Competence in Research (NCCR) ‘Molecular Oncology’, Lausanne, Switzerland
- ↵*Correspondence to: joerg.huelsken{at}epfl.ch
The intestine represents the most vigorously renewing, adult epithelial tissue that makes maintenance of its homeostasis a delicate balance between proliferation, cell cycle arrest, migration, differentiation, and cell death. These processes are precisely controlled by a network of developmental signalling cascades, which include Wnt, Notch, BMP/TGFβ, and Hedgehog pathways. A new, elegant study by Wong et al (2012) now adds Lrig1 as a key player in the control of intestinal homeostasis. As for epidermal stem cells, Lrig1 limits the size of the intestinal progenitor compartment by dampening EGF/ErbB‐triggered stem cell expansion.
There is an Article (March 2012) associated with this Have You Seen?.
Work from Kim Jensen's lab recently published in NCB establishes the crucial role of Lrig1 in the control of intestinal homeostasis.
- Copyright © 2012 European Molecular Biology Organization
Review
- Mechanisms regulating epidermal stem cells
- 1 Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles (ULB), Brussels, Belgium
- 2 WELBIO, Université Libre de Bruxelles (ULB), Brussels, Belgium
- ↵*Corresponding author. Interdisciplinary Research Institute (IRIBHM), Université Libre de Bruxelles (ULB), 808, Route de Lennik, BatC, C6‐130, Brussels 1070, Belgium. Tel.: +32 2 555 4190; Fax: +32 2 555 4655; E-mail: Cedric.Blanpain{at}ulb.ac.be
This review synthesizes recently published novel insights into the biological function and homeostatic control of epidermal stem cells.
- Received February 2, 2012.
- Accepted February 27, 2012.
- Copyright © 2012 European Molecular Biology Organization
Article
- Cohesin‐SA1 deficiency drives aneuploidy and tumourigenesis in mice due to impaired replication of telomeres
- Silvia Remeseiro1,
- Ana Cuadrado1,
- María Carretero1,
- Paula Martínez2,
- William C Drosopoulos3,
- Marta Cañamero4,
- Carl L Schildkraut3,
- María A Blasco2 and
- Ana Losada*,1
- 1 Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
- 2 Telomeres and Telomerase Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
- 3 Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY, USA
- 4 Comparative Pathology Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
- ↵*Corresponding author. Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain. Tel.: +34 917328000/ext. 3470; Fax: +34 917328033; E-mail: alosada{at}cnio.es
Mice lacking the cohesin subunit SA1 reveal a non‐redundant chromosome segregation role independent of centromeric cohesion maintenance. In contrast to the paralog SA2, whose inactivation in cancers promotes aneuploidy via bona fide cohesion defects, SA1‐mediated cohesion is required for accurate telomere replication and stabilization.
- Received September 12, 2011.
- Accepted January 9, 2012.
- Copyright © 2012 European Molecular Biology Organization
- A unique role of cohesin‐SA1 in gene regulation and development
- 1 Chromosome Dynamics Group, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
- 2 Bioinformatics Unit, Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
- ↵*Corresponding author. Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro 3, Madrid 28029, Spain. Tel.: +34 917328000/ext. 3470; Fax: +34 917328033; E-mail: alosada{at}cnio.es
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↵† These two authors contributed equally to this work
Loss of the cohesin subunit SA1 causes developmental defects and transcriptional deregulation resembling familial cohesin dysfunction disorders such as CdLS. SA1‐containing complexes are enriched at insulator and promoter regions, suggesting gene expression control specifically by SA1‐, not SA2‐cohesin.
- Received September 29, 2011.
- Accepted February 20, 2012.
- Copyright © 2012 European Molecular Biology Organization
- HIF1α induced switch from bivalent to exclusively glycolytic metabolism during ESC‐to‐EpiSC/hESC transition
- Wenyu Zhou1,2,
- Michael Choi2,3,
- Daciana Margineantu4,
- Lilyana Margaretha2,5,
- Jennifer Hesson2,6,
- Christopher Cavanaugh2,6,
- C Anthony Blau2,7,
- Marshall S Horwitz2,8,
- David Hockenbery*,4,
- Carol Ware*,2,6 and
- Hannele Ruohola‐Baker*,1,2,3
- 1 H Ruohola‐Baker Department of Biology, University of Washington, Seattle, WA, USA
- 2 Institute for Stem Cell and Regenerative Medicine (ISCRM), Seattle, WA, USA
- 3 Department of Biochemistry, University of Washington, Seattle, WA, USA
- 4 Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- 5 Molecular and Cellular Biology Program, University of Washington, Seattle, WA, USA
- 6 Department of Comparative Medicine, University of Washington, Seattle, WA, USA
- 7 Division of Hematology, University of Washington, Seattle, WA, USA
- 8 Department of Pathology, University of Washington, Seattle, WA, USA
- ↵*Corresponding authors: Department of Biochemistry, University of Washington, 815 MercerStreet, Seattle, WA 98195, USA. Tel.: +1 206 543 8468; Fax: +1 206 685 1357; E-mail: hannele{at}u.washington.edu or E-mail: dhockenb{at}fhcrc.org or E-mail: cware{at}u.washington.edu
Metabolic analyses on naive ESCs versus primed EpiSCs reveal a functional switch fromoxidative phosphorylation to glycolysis. Differential gene expression definesHIF1α and reduced complex IV activity as crucial metabolic regulators duringstem‐cell differentiation.
- Received November 2, 2011.
- Accepted February 28, 2012.
- Copyright © 2012 European Molecular Biology Organization
- Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice
- Pedro M Quirós1,
- Andrew J Ramsay1,
- David Sala2,3,4,
- Erika Fernández‐Vizarra5,6,
- Francisco Rodríguez1,
- Juan R Peinado1,†,
- Maria Soledad Fernández‐García7,
- José A Vega8,
- José A Enríquez6,9,
- Antonio Zorzano2,3,4 and
- Carlos López‐Otín*,1
- 1 Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Oviedo, Spain
- 2 Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
- 3 Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain
- 4 CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Spain
- 5 IIS Aragón, Unidad de Investigación Traslacional I+CS, Hospital Universitario Miguel Servet, Zaragoza, Spain
- 6 Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias, Universidad de Zaragoza, Zaragoza, Spain
- 7 Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias, Oviedo, Spain
- 8 Departamento de Morfología y Biología Celular, Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
- 9 Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain
- ↵*Corresponding author. Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Oviedo, 33006 Oviedo, Spain. Tel.: +34 985 104201; Fax: +34 985 103564; E-mail: clo{at}uniovi.es
The metalloprotease OMA1 is involved in the proteolytic inactivation of the dynaminrelated GTPase OPA1, a key regulator of mitochondrial dynamics. OMA1 knockout mice indicate that mitochondrial quality control and dynamics impact energy metabolism, in particular under metabolic stress.
- Received September 20, 2011.
- Accepted February 17, 2012.
- Copyright © 2012 European Molecular Biology Organization
- Tightening of the ATP‐binding sites induces the opening of P2X receptor channels
- Ruotian Jiang1,†,
- Antoine Taly1,†,
- Damien Lemoine1,
- Adeline Martz1,
- Olivier Cunrath1 and
- Thomas Grutter*,1
- 1 Faculté de Pharmacie, Laboratoire de Biophysicochimie des Récepteurs Canaux, UMR 7199 CNRS, Conception et Application de Molécules Bioactives, Université de Strasbourg, Illkirch, France
- ↵*Corresponding author. Faculté de Pharmacie, Laboratoire de Biophysicochimie des Récepteurs Canaux, UMR 7199 CNRS, Conception et Application de Molécules Bioactives, Université de Strasbourg, 67400 Illkirch, France. Tel.:+333 68 85 41 57; Fax:+333 68 85 43 06; E-mail: grutter{at}unistra.fr
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↵† These authors contributed equally to this work
P2X receptors are ATP‐gated ion channels involved in many processes, including synaptic transmission and sensory signalling, but their gating mechanism is still ill understood. This study reveals that extracellular ATP opens the channel by tightening nucleotide‐binding sites that are shaped like open ‘jaws’
- Received December 20, 2011.
- Accepted March 6, 2012.
- Copyright © 2012 European Molecular Biology Organization
- Solution single‐vesicle assay reveals PIP2‐mediated sequential actions of synaptotagmin‐1 on SNAREs
- Jae‐Yeol Kim1,†,
- Bong‐Kyu Choi2,†,
- Mal‐Gi Choi3,
- Sun‐Ae Kim4,
- Ying Lai4,
- Yeon‐Kyun Shin*,4,5 and
- Nam Ki Lee*,1,2
- 1 Department of Physics, Pohang University of Science and Technology, Pohang, Korea
- 2 School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Korea
- 3 Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Korea
- 4 Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA, USA
- 5 Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, Korea
- ↵*Corresponding authors: Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011‐3111, USA. Tel.: +1 515 294 2530; Fax: +1 515 294 0453; E-mail: colishin{at}iastate.eduDepartment of Physics, Pohang University of Science and Technology, Pohang 790‐784, Korea. Tel.: +82 54 279 2097; Fax: +82 54 279 3099; E-mail: nklee{at}postech.ac.kr
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↵† These authors contributed equally to this work
Synaptotagmin‐1 (Syt1) is a major calcium sensor required for SNARE‐mediated synaptic vesicle fusion. ALEX, a single‐molecule technique capable of characterizing subpopulations of fusion intermediates, reveals distinct roles of Syt1 in vesicle docking and fusion with the plasma membrane.
- Received September 8, 2011.
- Accepted February 8, 2012.
- Copyright © 2012 European Molecular Biology Organization
- Munc18‐1 mutations that strongly impair SNARE‐complex binding support normal synaptic transmission
- Marieke Meijer1,†,
- Pawel Burkhardt2,†‡,
- Heidi de Wit1,
- Ruud F Toonen1,
- Dirk Fasshauer*,2,3 and
- Matthijs Verhage*,1
- 1 Department of Functional Genomics and Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam and VU University Medical Center, Amsterdam, The Netherlands
- 2 Research Group Structural Biochemistry, Department of Neurobiology, Max‐Planck‐Institute for Biophysical Chemistry, (MPIbpc), Göttingen, Germany
- 3 Department of Cellular Biology and Morphology, University of Lausanne, Lausanne, Switzerland
- ↵*Corresponding authors: Research Group Structural Biochemistry, Department of Neurobiology, Max‐Planck‐Institute for Biophysical Chemistry, (MPIbpc), Am Fassberg 11, Göttingen 37077, Germany; Tel.:+41 21 6925287; Fax:+41 21 6925105; E-mail: Dirk.Fasshauer{at}unil.chDepartment of Functional Genomics and Department of Clinical Genetics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University Amsterdam and VU University Medical Center, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands. Tel.:+31 20 5986936; Fax:+31 20 5986926; E-mail: matthijs.verhage{at}cncr.vu.nl
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↵† These authors contributed equally to this work
Synaptic vesicle exocytosis depends on the SM protein Munc18‐1, but its precise role is controversial. Munc18‐1 mutants reveal that the protein acts primarily before/during SNARE complex assembly rather than at the level of assembled fusion complexes.
- Received January 11, 2012.
- Accepted February 28, 2012.
- Copyright © 2012 European Molecular Biology Organization
- Bat3 facilitates H3K79 dimethylation by DOT1L and promotes DNA damage‐induced 53BP1 foci at G1/G2 cell‐cycle phases
- ↵*Corresponding author. Department of Pharmacology and Cancer Biology, Duke University Medical Center, Research Drive LSRC C215, Durham, NC 27710, USA. Tel.: +1 919 681 4861; Fax: +1 919 681 7152; E-mail: wang0011{at}mc.duke.edu
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↵† These two authors contributed equally to this work
The human DNA repair protein 53BP1 is targeted to sites of DNA damage by several histone methylation marks. Bat3 aids generation of H3K79 methyl marks outside of S‐phase by recruiting the methyltransferase DOT1L through a ubiquitin‐like domain.
- Received June 8, 2011.
- Accepted February 7, 2012.
- Copyright © 2012 European Molecular Biology Organization
- Mcm10 plays an essential role in origin DNA unwinding after loading of the CMG components
- ↵*Corresponding author. Department of Biological Sciences, Graduate School of Science, 1‐1 Machikaneyama‐cho, Toyonaka, Osaka 560‐0043, Japan. Tel.: +81 6 6850 5432; Fax: +81 6 6850 5440; E-mail: masukata{at}bio.sci.osaka-u.ac.jp
Acute removal of the fission yeast Mcm10 replication protein via an auxin‐inducible degron shows that it activates DNA unwinding and initiation independent of assembling the Cdc45–Mcm2‐7–GINS helicase complex.
- Received December 2, 2011.
- Accepted February 27, 2012.
- Copyright © 2012 European Molecular Biology Organization
- Mcm10 associates with the loaded DNA helicase at replication origins and defines a novel step in its activation
- Frederick van Deursen1,
- Sugopa Sengupta1,
- Giacomo De Piccoli1,
- Alberto Sanchez‐Diaz1,† and
- Karim Labib*,1
- ↵*Corresponding author. Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. Tel.: +44 161 446 8168; Fax: +44 161 446 3109; E-mail: klabib{at}picr.man.ac.uk
The replication factor Mcm10 is required for activation of the Mcm2‐7 replicative helicase loaded at replication origins, while its acute depletion does not affect helicase assembly or interaction with DNA polymerase alpha in budding yeast.
- Received December 2, 2011.
- Accepted February 28, 2012.
- Copyright © 2012 European Molecular Biology Organization
- EBV and human microRNAs co‐target oncogenic and apoptotic viral and human genes during latency
- Kasandra J Riley1,
- Gabrielle S Rabinowitz1,2,
- Therese A Yario1,
- Joseph M Luna2,
- Robert B Darnell2 and
- Joan A Steitz*,1
- 1 Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, USA
- 2 Laboratory of Molecular Neuro‐Oncology, Howard Hughes Medical Institute, Rockefeller University, New York, NY, USA
- ↵*Corresponding author. Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, 295 Congress Avenue, BCMM136, New Haven, CT 06536, USA. Tel.:+203 737 4418; Fax:+203 624 8213; E-mail: joan.steitz{at}yale.edu
The global analysis of miRNA targets in EBV transformed B‐cells shows that viral miRNAs mostly target cellular and not viral genes, many of which are also targeted by the oncogenic human miR‐17∼92 cluster.
- Received October 6, 2011.
- Accepted February 16, 2012.
- Copyright © 2012 European Molecular Biology Organization
- Crystal structure of Cwc2 reveals a novel architecture of a multipartite RNA‐binding protein
- Jana Schmitzová1,2,
- Nicolas Rasche1,
- Olexander Dybkov1,
- Katharina Kramer1,3,
- Patrizia Fabrizio1,
- Henning Urlaub1,3,4,
- Reinhard Lührmann*,1 and
- Vladimir Pena*,1,2
- 1 Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
- 2 Macromolecular Crystallography Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
- 3 Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany
- 4 Department of Clinical Chemistry, Bioanalytics, University Medical Center Göttingen, Göttingen, Germany
- ↵*Corresponding authors: Macromolecular Crystallography Group, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen 37077, Germany. Tel.: +49 551 201 1046; Fax: +49 551 201 1197; E-mail: Vladimir.Pena{at}mpi-bpc.mpg.deDepartment of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, Göttingen 37077, Germany. Tel.: +49 551 201 1405; Fax: +49 551 201 1197; E-mail: Reinhard.Luehrmann{at}mpi-bpc.mpg.de
Splicing factor Cwc2 positions pre‐mRNA and U6 RNA during the activation of the spliceosome. The structure of Cwc2 and mapping of the Cwc2–U6 snRNA interaction provide insight into the spliceosome catalytic centre.
- Received September 18, 2011.
- Accepted February 14, 2012.
- Copyright © 2012 European Molecular Biology Organization
