SMC Proteins & Chromosome Dynamics

The Gruber lab at the Department of Fundamental Microbiology (DMF) in Lausanne studies elementary processes in the cell using microbial model organisms. Our main focus is on chromosome organization and genome maintenance. Find out what we do and who we are.

  • How are genomes organized in the cell ?
  • How are chromosomes segregated during cell division ?
  • How is DNA damage repaired ?
Electron micrograph showing part of a decondensed mitotic chromosome. CIL: 11023

Research

DNA Organization, Dynamics & Repair

Folding chromosomes by DNA loop extrusion

Cells organize and compact long and flexible chromosomal DNA molecules to precisely control gene expression patterns, DNA repair processes and DNA recombination events, and to faithfully segregate chromosomes during cell division. What determines chromosome superstructure and how it impacts upon genome expression and genome maintenance are major open questions in biology. We aim to elucidate fundamental principles of chromosome folding by studying microbial model organisms including the Gram-positive bacterium Bacillus subtilis and budding yeast Saccharomyces cerevisiae.

SMC proteins & DNA loop extrusion

Dynamic SMC architecture

Our work focuses on two widely distributed factors in chromosome organization: SMC protein complexes and ParABS systems. SMC complexes form multi-subunit ATPases with a characteristic ring topology. They organize DNA as genome linkers by clamping together pairs of chromosomal DNA segments. To uncover how they bring together the “right” pairs of DNA double helices, we investigate how SMC complexes interact with DNA and chromosomes. The emerging view is that DNA loop extrusion by SMC DNA motors plays the key role in the remarkable process of chromosome organization. In bacteria, SMC complexes load onto chromosomes at defined entry sites — parS sites — and then translocate onto flanking DNA helping to shape entire bacterial chromosomes. We want to understand how local SMC loading and subsequent DNA translocation brings about global chromosome folding.

ParABS & cellular regulation

ParB CTPase self-loading at a parS site.

ParABS systems promote chromosome segregation and plasmid maintenance in many bacteria and some archaea. It also supports additional regulatory functions in the cell. ParABS systems work by ParB protein binding to centromeric parS sequences to form large nucleoprotein complexes that act in concert with specific ATPases, ParA and Smc, to partition plasmid and chromosome copies. We have recently discovered that ParB proteins are enzymes — the first known CTP hydrolases — which form DNA sliding clamps that self-load onto parS DNA. We are particularly interested how ParB CTP binding and hydrolysis act together with ParA and Smc ATPases to promote chromosome organization and segregation in bacteria.

Our approach

Knowledge of the architecture and structure of macromolecular assemblies is often a prerequisite for a basic mechanistic understanding. We integrate genetics, molecular & cell biology and biochemistry with structural biology approaches to reveal the molecular basis for protein function and cellular activity.

We investigate protein-DNA complexes and DNA organization in vitro using an array of biophysical techniques and structural biology and in vivo for example by ChIP-Seq, Hi-C, directed or random mutagenesis and site-specific cross-linking. Bacillus subtilis develops natural competence under starvation and can readily be genetically manipulated, supporting easy and high-throughput allelic replacements.

New focus

In relatively new lines of investigation, we are focusing on the roles of SMC and SMC-like proteins (Rad50, RecN and the Smc5/6 complex) in the maintenance of DNA integrity in bacteria and eukaryotes.

Members

aniagrey Anna Anchimiuk

anna.anchimiuk[a]unil.ch
+41-21-692-5611

2012-2014 – M. Sc. Biotechnology – University of Gdansk and Medical University of Gdansk

Hammam Antar

hammam.antar[a]unil.ch
+41-21-692-5611

2017-2019 – M. Sc. Immunology, Microbiology & Infections Diseases – University of Grenoble Alpes, France

Florian Bock

florianpatrick.bock[a]unil.ch
+41-21-692-5611

2013-2016 – M. Sc. Biochemistry – Ludwig Maximilians University, Munich

Eryk Dunski

eryk.dunski[a]unil.ch
+41-21-692-5611

2016-2018 – M. Sc. Biology-Biotechnology – University of Copenhagen, Denmark

Stephan Gruber

Short CV

stephan gruber unil ch
+41-21-692-5601

OrcID, ResearchGate, Google Scholar

Young-Min Soh

youngmin.soh[a]unil.ch
+41-21-692-5611

2010-2015 – Ph. D. Structural Biology – Oh lab, KAIST, Daejeon, Korea
2005-2009 – B. Sc. Biology, Department of Biological Sciences, KAIST, Daejeon, Korea

Michael Taschner

michael.taschner[a]unil.ch
+41-21-692-5611

2010-2017 – Postdoc – Lorentzen lab, Max Planck Institute of Biochemistry, Munich, Germany
2005-2009 – Ph. D. Biochemistry – Svejstrup lab, University College London, UK
2000-2004 – Diploma Biology – University of Vienna, Austria

Roberto Vazquez Nunez

robertojareth.vazqueznunez[a]unil.ch
+41-21-692-5611

2013-2015 – M. Sc. Biochemical Sciences – National Autonomous University, Mexico

Former lab members

Alrun Basfeld, Intern, now @ Lohmann & Rauscher, Cologne, Germany

Mélanie Beraud, Postdoctoral fellow, now senior technician @ Université de Mons, Mons, Belgium

Martin Blettinger, Technician, now @ Hexal Sandoz, Munich, Germany

Frank Bürmann, PhD student, now Postdoc @ MRC-LMB Cambridge, UK

Marie-Laure Diebold-Durand, Postdoctoral fellow, now @IGBMC Strasbourg, France

Alexandre Durand, Postdoctoral fellow, now EM Facility Manager – Inserm @IGBMC Strasbourg, France

Victor Gimenez -Oya, Postdoctoral fellow, now @ LMU Munich, Germany

Daniel Meyer, Technician, now @ Max Planck Institute for Quantum Optics, Munich, Germany

Anita Minnen, PhD student, now Postdoc @ Max Planck Institute of Biochemistry, Munich, Germany

Laura Ruiz Avila, Postdoctoral fellow, currently on parental leave, Munich, Germany

Chris Toseland, Postdoctoral fellow, now group leader @ University of Kent, UK

Larissa Wilhelm, PhD student, now @ Bristol-Meyers Squibb, Munich, Germany

Publications

2019

  • Soh Y.-M., Davidson I.F., Zamuner S., Basquin J., Taschner M., Bock F.P., Veening J.-W., De Los Rios P., Peters J.-M., Gruber S.*, 2019. Self-organization of parS centromeres by the ParB CTP hydrolase.
    Science

    360(6469) p. 1129-1133 [Pubmed] [DOI] [PDB: 6SDK] [PDF] [F1000 recommendation] [Perspective by Barbara Funnell]
  • Vazquez Nunez R., Ruiz Avila L.B., Gruber S.*, 2019. Transient DNA occupancy of the SMC interarm space in prokaryotic condensin.
    Molecular Cell

    75(5) p. 1-15 [Pubmed] [DOI] [Preview by Tomoko Nishiyama]
    preprint [BioRxiv]
  • Marko J.F.*, De Los Rios P., Barducci A., Gruber S., 2019. DNA-segment-capture model for loop extrusion by structural maintenance of chromosome (SMC) protein complexes.
    Nucleic Acids Research

    gkz497 [Pubmed] [DOI]
    preprint [BioRxiv]
  • Diebold-Durand M.L., Bürmann F., Gruber S.*, 2019. High-throughput allelic replacement screening in Bacillus subtilis.
    Methods in Molecular Biology

    2004 p. 49-61 [Pubmed] [DOI] [PDF]

2018

  • Pfeiffer F., Zamora-Lagos M.-A., Blettinger M., Yeroslavic A., Dahl A., Gruber S.*, Habermann B.H.*, 2018. The complete and fully assembled genome sequence of Aeromonas salmonicida subsp. pectinolytica and its comparative analysis with other Aeromonas species: investigation of the mobilome in environmental and pathogenic strains.
    BMC Genomics
    19(1):20 [Pubmed] [DOI]
  • Gruber S., 2018. SMC complexes sweeping through the chromosome: Going with the flow and against the tide.
    Current Opinion in Microbiology
    42:96-103 [Pubmed] [DOI] [PDF]
  • Stockmar I., Feddersen H., Cramer K., Gruber S., Jung K., Bramkamp M.*, Shin J.Y.* 2018. Optimization of sample preparation and green color imaging using the mNeonGreen fluorescent protein in bacterial cells for photoactivated localization microscopy.
    Scientific Reports
    8(1): 10137 [Pubmed] [DOI]

2017

  • Diebold-Durand M.L., Lee H., Ruiz Avila L., Noh H., Shin H.-C., Im H., Bock F.P., Bürmann F., Durand A., Basfeld A., Ham S., Basquin J., Oh B.-H.*, Gruber S.*, 2017. Structure of full-length SMC and rearrangements required for chromosome organization.
    Molecular Cell
    67(2) p. 334-347 [DOI] [Web of Science] [Pubmed] [PDB: 5NMO, 5NNV]
  • Bürmann F., Basfeld A., Vazquez Nunez R., Diebold-Durand M.L., Wilhelm L., Gruber S.*, 2017. Tuned SMC arms drive chromosomal loading of prokaryotic condensin.
    Molecular Cell
    65(5) p. 861-872 [DOI] [Web of Science] [Pubmed] [F1000 recommendation]
  • Gruber S., 2017. Shaping Chromosomes by DNA Capture and Release: Gating the SMC Rings.
    Current Opinion in Cell Biology
    46:87-93 [DOI] [Web of Science] [Pubmed] [PDF]
  • Wilhelm L., Gruber S., 2017. A Chromosome Co-Entrapment Assay to Study Topological Protein–DNA Interactions.
    Methods in Molecular Biology
    1624 p. 117-126 [DOI] [Web of Science] [Pubmed] [PDF]. An updated version of the protocol (using agarose microbeads instead of agarose plugs) is available here: [DOI].

2016

  • Minnen A., Bürmann F., Wilhelm L., Anchimiuk A., Diebold-Durand M.L., Gruber S.*, 2016. Control of Smc Coiled Coil Architecture by the ATPase Heads Facilitates Targeting to Chromosomal ParB/parS and Release onto Flanking DNA.
    Cell Reports
    14(8) pp. 2003-2016 [DOI] [Web of Science] [Pubmed]
  • Haering C.H., Gruber S., 2016. SnapShot: SMC Protein Complexes Part I.
    Cell
    164(1-2) pp. 326-6.e1 [DOI] [Web of Science] [Pubmed]
  • Haering C.H., Gruber S., 2016. SnapShot: SMC Protein Complexes Part II.
    Cell
    164(4) p. 818.e1 [DOI] [Web of Science] [Pubmed]
  • Wilhelm L., Gruber S., 2016. Chromosom in Schleifen: SMC-Komplexe als molekulare Kabelbinder?
    BioSpektrum
    22(4) p. 356-358 [DOI] [PDF]

2015

  • Soh Y.M., Bürmann F., Shin H.C., Oda T., Jin K.S., Toseland C.P., Kim C., Lee H., Kim S.J., Kong M.S., Durand-Diebold M.L., Kim Y.G., Kim H.M., Lee N.K., Sato M., Oh B.H.*, Gruber S.*, 2015. Molecular basis for SMC rod formation and its dissolution upon DNA binding.
    Molecular Cell
    57(2) pp. 290-303 [DOI] [Web of Science] [Pubmed]
  • Wilhelm L., Bürmann F., Minnen A., Shin H.C., Toseland C.P., Oh B.H., Gruber S.*, 2015. SMC condensin entraps chromosomal DNA by an ATP hydrolysis dependent loading mechanism in Bacillus subtilis.
    Elife
    4:e06659 [DOI] [Web of Science] [Pubmed]
  • Palecek J.J.*, Gruber S.*, 2015. Kite Proteins: a Superfamily of SMC/Kleisin Partners Conserved Across Bacteria, Archaea, and Eukaryotes.
    Structure
    23(12) pp. 2183-2190. [DOI] [Web of Science] [Pubmed]
  • Kang H.A., Shin H.C., Kalantzi A.S., Toseland C.P., Kim H.M., Gruber S., Peraro M.D., Oh B.H.*, 2015. Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination.
    Nucleic Acids Research
    43(7) pp. 3841-3856 [DOI] [Web of Science] [Pubmed]
  • Attaiech L., Minnen A., Kjos M., Gruber S., Veening J.W.*, 2015. The ParB-parS Chromosome Segregation System Modulates Competence Development in Streptococcus pneumoniae.
    Mbio
    6(4) pp. e00662 [DOI] [Web of Science] [Pubmed]
  • Bürmann F., Gruber S., 2015. SMC condensin: promoting cohesion of replicon arms.
    Nature Structural & Molecular Biology
    22(9) pp. 653-655 [DOI] [Web of Science] [Pubmed] [PDF] [PDB: 3ZGX]

2014

  • Gruber S.*, Veening J.W., Bach J., Blettinger M., Bramkamp M., Errington J.*, 2014. Interlinked sister chromosomes arise in the absence of condensin during fast replication in B. subtilis.
    Current Biology
    24(3) pp. 293-298 [DOI] [Web of Science] [Pubmed]
  • Gligoris T.G., Scheinost J.C., Bürmann F., Petela N., Chan K.L., Uluocak P., Beckouët F., Gruber S., Nasmyth K.*, Löwe J.*, 2014. Closing the cohesin ring: structure and function of its Smc3-kleisin interface.
    Science
    346(6212) pp. 963-967 [DOI] [Web of Science] [Pubmed]
  • Gruber S., 2014. Multilayer chromosome organization through DNA bending, bridging and extrusion.
    Current Opinion In Microbiology
    22 pp. 102-110 [DOI] [Web of Science] [Pubmed]

2013

  • Bürmann F., Shin H.C., Basquin J., Soh Y.M., Giménez-Oya V., Kim Y.G., Oh B.H.*, Gruber S.*, 2013. An asymmetric SMC-kleisin bridge in prokaryotic condensin.
    Nature Structural & Molecular Biology
    20(3) pp. 371-379 [DOI] [Web of Science] [Pubmed] [PDF]

2011

  • Gruber S., 2011. MukBEF on the march: taking over chromosome organization in bacteria?
    Molecular Microbiology
    81(4) pp. 855-859 [DOI] [Web of Science] [Pubmed]
  • Minnen A., Attaiech L., Thon M., Gruber S.*, Veening J.W.*, 2011. SMC is recruited to oriC by ParB and promotes chromosome segregation in Streptococcus pneumoniae.
    Molecular Microbiology
    81(3) pp. 676-688 [DOI] [Web of Science] [Pubmed]

2009

  • Gruber S., Errington J.*, 2009. Recruitment of condensin to replication origin regions by ParB/SpoOJ promotes chromosome segregation in B. subtilis.
    Cell
    137(4) pp. 685-696 [DOI] [Web of Science] [Pubmed]

2006

  • Gruber S., Arumugam P., Katou Y., Kuglitsch D., Helmhart W., Shirahige K., Nasmyth K.*, 2006. Evidence that loading of cohesin onto chromosomes involves opening of its SMC hinge.
    Cell
    127(3) pp. 523-537 [DOI] [Web of Science] [Pubmed]
  • Arumugam P., Nishino T., Haering C.H., Gruber S., Nasmyth K.*, 2006. Cohesin’s ATPase activity is stimulated by the C-terminal Winged-Helix domain of its kleisin subunit.
    Current Biology
    16(20) pp. 1998-2008 [DOI] [Web of Science] [Pubmed]

2004

  • Riedel C.G.*, Gregan J., Gruber S., Nasmyth K., 2004. Is chromatin remodeling required to build sister-chromatid cohesion?
    Trends In Biochemical Sciences
    29(8) pp. 389-392 [DOI] [Web of Science] [Pubmed] [PDF]

2003

  • Gruber S., Haering C.H., Nasmyth K.*, 2003. Chromosomal cohesin forms a ring.
    Cell
    112(6) pp. 765-777 [DOI] [Web of Science] [Pubmed]
  • Arumugam P., Gruber S., Tanaka K., Haering C.H., Mechtler K., Nasmyth K.*, 2003. ATP hydrolysis is required for cohesin’s association with chromosomes.
    Current Biology
    13(22) pp. 1941-1953 [DOI] [Web of Science] [Pubmed]
  • Buonomo S.B., Rabitsch K.P., Fuchs J., Gruber S., Sullivan M., Uhlmann F., Petronczki M., Tóth A., Nasmyth K.*, 2003. Division of the nucleolus and its release of CDC14 during anaphase of meiosis I depends on separase, SPO12, and SLK19.
    Developmental Cell
    4(5) pp. 727-739 [DOI] [Web of Science] [Pubmed]