SMC Proteins & Chromosome Dynamics

The Gruber lab investigates molecular machines that act on DNA to ensure the integrity of genetic information and to promote defence from invasive genetic elements. By all means.

  • How are genomes organized?
  • How are chromosomes segregated during cell division?
  • How is DNA damage repaired?
  • How is non-self DNA recognized and eliminated?

We are part of the Department of Fundamental Microbiology (@DMF_UNIL) at the Faculty of Biology and Medicine, the University of Lausanne. Find out who we are and what we do. Follow us .

Electron micrograph showing part of a decondensed mitotic chromosome. CIL: 11023

In science, truth always wins.‘ Max Perutz

The two most powerful warriors are patience and time.‘ Leo Tolstoy

There is no substitute for being first‘ John F Marko

Research

Organizing DNA for Segregation and Repair

Folding chromosomes by DNA loop extrusion

Cells organize and compact the long and flexible DNA molecules within chromosomes to precisely control gene expression patterns, to support DNA repair processes and DNA recombination events, and to faithfully segregate chromosomes during cell division. However, the underlying principles of chromosome folding and how they impact genome expression and maintenance are still poorly understood. Our research aims to shed light on these fundamental processes by studying microbial model organisms including bacteria and budding yeast

Key factors in chromosome folding: The SMC ATPase complexes

Dynamic SMC architecture

Our research focuses on the multi-subunit SMC ATPase complexes, which play a crucial role in organizing chromosomes by bringing together distal segments of a chromosome. The current theory is that these complexes are responsible for actively extruding DNA loops through the use of the SMC DNA motor. These motors are able to take large steps along the DNA and bypass obstacles, while also maintaining directionality over long periods of time. To gain a better understanding of the mechanisms behind this process, we are studying bacterial SMC complexes and the yeast Smc5/6 complex using biochemical techniques and cryo-electron microscopy at the Dubochet Center for Imaging in Lausanne (@DCI_EM). Our work has led to the development of the DNA segment capture model, which we are now testing.

SMC Wadjet systems in bacterial immunity

Model for plasmid DNA elimination by Wadjet SMC.

Wadjet systems are derivative SMC complexes that play a role in bacterial immunity, rather than in chromosome folding. We and others have recently shown that these JetABCD complexes eliminate plasmids by cleaving the DNA. We are interested in understanding how the Wadjet complexes specifically recognize and target smaller circular DNA molecules, while sparing the host chromosome from processing. The eukaryotic Smc5/6 complexes have been shown to play an apparently related role in defense against infection by viruses (HBV, EBV and others). We are working to understand how these activities in viral and plasmid defense are related to one another and to the more canonical functions of SMC complexes in genome folding and maintenance. Recently, we have also started investigating other bacterial defense systems that act on DNA and share similarities with chromosomal machinery.

ParABS & cellular regulation

ParB CTPase self-loading at a parS site.

ParABS systems are important for promoting chromosome segregation and plasmid maintenance in many bacteria and some archaea, as well as for supporting additional regulatory functions within the cell. These systems work by binding ParB proteins to centromeric parS sequences to form large nucleoprotein complexes that interact 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 in how the combination of ParB CTP binding and hydrolysis with ParA and Smc ATPases promotes chromosome organization and segregation in bacteria.

Our approach

A deep understanding of the architecture and structure of macromolecular assemblies is often essential for gaining a mechanistic understanding of their function. Our research combines genetics, molecular and cell biology, biochemistry, and structural biology to reveal the molecular basis of protein function and cellular activity. We use a range of biophysical techniques and structural biology to investigate protein-DNA complexes and DNA organization in vitro, as well as in vivo techniques such as ChIP-Seq, Hi-C, directed or random mutagenesis, and site-specific cross-linking. By combining these approaches, we hope to gain insights into the underlying mechanisms of these complex systems.

New focus?

We are always open to exploring new areas of research, including the roles of other SMC and SMC-like proteins (such as Rad50 and RecN) in maintaining DNA integrity in both bacteria and eukaryotes.

Members

 

Hammam Antar

 

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

2017-2019 – M. Sc. Immunology, Microbiology & Infectious Diseases (IMD) – University of Grenoble Alpes, France

Joe Dickinson

 

joe.dickinson[a]unil.ch
+41-21-692-5611

2020-2022 – M. Sc. Molecular Life Sciences – University of Lausanne, Switzerland

Ophélie Gosselin

 

ophélie.gosselin[a]unil.ch
+41-21-692-5611

2017-2019 – M. Sc. Biochemistry, Molecular and Cellular Biology – UC Louvain, Belgium

Stephan Gruber

 

Short CV

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

OrcID, WebOfScienceResearchGate, Google Scholar

Maya Houmel

 

maya.houmel[a]unil.ch
+41-21-692-5611

2018-2020 – M. Sc. Genetics,  Magistère Européen de Génétique, University of Paris, France

Franziska Kemter – DFG Postdoc

 

franziska.kemter[a]unil.ch
+41-21-692-5611

2014-2019 – Ph. D. and Postdoc, Chromosome Biology – Waldminghaus lab, SYNMICRO, Philipps-University Marburg, Germany
2012-2014 – M. Sc. Molecular and Cellular Biology – Philipps-University Marburg, Germany

Yan Li

 

yan.li[a]unil.ch
+41-21-692-5611

2015-2019 – Ph. D. , Panne lab, EMBL Grenoble, France
2010-2013 – M. Sc. Structural Biology – University of the Chinese Academy of Sciences, Shanghai, China

Hon-Wing Liu – EMBO Postdoc

 

hon-wing.liu[a]unil.ch
+41-21-692-5611

2015-2020 – Ph. D. , Uhlmann lab, The Francis Crick Institute, London, UK
2011-2015 – MA M. Sc. Biochemistry – University of Cambridge, UK

Nicolas Pellaton

 

nicolas.pellaton[a]unil.ch
+41-21-692-5611

2020- 2021 – M. Sc. student, University of Lausanne
2017-2020 – B. Sc. Biology, University of Lausanne, Switzerland

Florian Roisné-Hamelin – EMBO Postdoc

 

florian.roisne-hamelin[a]unil.ch
+41-21-692-5611

2016-2021 – Ph. D., Marcand lab,  Institut de Biologie François Jacob, CEA, Paris, France

2014-2016 – M. Sc. Genetics & Cell Biology- University of Lyon 1, France

Michael Taschner – Research scientist

 

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, UCL, UK
2000-2004 – Diploma Biology – University of Vienna, Austria

Former lab members

Anna Anchimiuk, PhD student, now @ Roche, Switzerland

Alrun Basfeld, Intern, now @ WuXi Biologics, Leverkusen, Germany

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

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

Florian Bock, PhD student, now @ Venning lab, Lausanne, Switzerland

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, now @ Extedo, Munich, Germany

Jae Shin, Postdoc, now Senior Researcher @ NanoLund, Sweden

Young-Min Soh, Postdoctoral fellow, now fellow @ NIH, US

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

Roberto Vazquez Nunez, PhD student, now Postdoctoral fellow @ NIH, US

Larissa Wilhelm, PhD student, now @ Novartis, Vienna, Austria

Publications

Preprints

  • Tišma M., Bock F.P., Kerssemakkers J., Japaridze A., Gruber S., Dekker C.*, 2023. Direct observation of a crescent-shape chromosome in Bacillus subtilis.
    preprint [BioRxiv]

2023

  • Taschner M., Gruber S.*, 2023. DNA segment capture by Smc5/6 holo-complexes.
    Nature Structural & Molecular Biology
    10.1038/s41594-023-00956-2 [Pubmed] [DOI]
    preprint [BioRxiv]

2022

  • Liu H. W., Roisné-Hamelin F., Beckert B., Li Y., Myasnikov A., Gruber S.*, 2022. DNA-measuring Wadjet SMC ATPases restrict smaller circular plasmids by DNA cleavage.
    Molecular Cell
    Vol 82, Issue 24 [Pubmed] [DOI]
    preprint [BioRxiv]
  • Roberts D. M., Anchimiuk A., Kloosterman T. G., Murray H., Wu L. J, Gruber S., Errington J.*, 2022. Chromosome remodelling by SMC/Condensin in B. subtilis is regulated by Soj/ParA during growth and sporulation.
    PNAS
    Vol 40, Issue 9 [Pubmed] [DOI]
    preprint [BioRxiv]
  • Bock F. P., Liu H. W., Anchimiuk A., Diebold-Durand M.-L., Gruber S.*, 2022. A joint-ParB interface promotes Smc DNA recruitment.
    Cell Reports
    Vol 119, Issue 41 [Pubmed] [DOI]
    preprint [BioRxiv]
  • Tisma M., Panoukidou M., Antar H., Soh Y.-M., Barth R., Pradhan B., van der Torre J., Michieletto D., Gruber S., Dekker C.*, 2022. ParB proteins can bypass DNA-bound roadblocks by dimer-dimer recruitment.
    Science Advances
    Vol 8, Issue 26 [Pubmed] [DOI]
    preprint [BioRxiv]
  • Nomidis S.S., Carlon E., Gruber S., Marko J. F.*, 2022. DNA tension-modulated translocation and loop extrusion by SMC complexes revealed by molecular dynamics simulations.
    Nucleic acids research
    gkac268 [Pubmed] [DOI]
    preprint [BioRxiv]

2021

  • Antar H.°, Soh Y.-M.°, Zamuner S., Bock F. P., Anchimiuk A., De Los Rios P., Gruber S.*, 2021. Relief of ParB autoinhibition by parS DNA catalysis and ParB recycling by CTP hydrolysis promote bacterial centromere assembly.
    Science Advances
    Vol 7, Issue 41 [Pubmed] [DOI]
    preprint [BioRxiv]
  • Taschner M., Basquin J., Steigenberger B., Schaefer I., Soh Y.-M., Basquin C., Lorentzen E., Räschle M., Scheltema R. A., Gruber S.*, 2021. Nse5/6 inhibits the Smc5/6 ATPase and modulates DNA substrate binding.
    EMBO Journal
    e107807 [Pubmed] [DOI]
    preprint [BioRxiv]
  • Anchimiuk A., Lioy V. S., Minnen A., Boccard F., Gruber S.*, 2021. A low Smc flux avoids collisions and facilitates chromosome organization in B. subtilis.
    eLife
    65467 [Pubmed] [DOI]
    preprint [BioRxiv]
  • Gallay C.°, Sanselicio S.°, Anderson M. E.,  Soh Y.-M., Liu X., Stamsas G. A., Pelliciari S., van Raaphorst R., Dénéréaz J., Kjos M., Murray H., Gruber S., Grossman A. D., Veening J.-W.*, 2021. CcrZ is a pneumococcal spatiotemporal cell cycle regulator that interacts with FtsZ and controls DNA replication.
    Nature Microbiology
    021-00949-1 [Pubmed] [DOI]
    preprint [BioRxiv]
  • Vazquez Nunez R. J.°, Polyhach Y.°, Soh Y.-M., Jeschke G., Gruber S.*, 2021. Gradual opening of Smc arms in prokaryotic condensin.
    Cell Reports
    35(4) 109051 [Pubmed] [DOI]
    preprint [BioRxiv]

2020

  • Soh Y.-M., Basquin J., Gruber S.*, 2020. A rod conformation of the Pyrococcus furiosus Rad50 coiled coil.
    Proteins
    prot.26005 [Pubmed] [DOI] [PDB: 6ZFF]
    preprint [BioRxiv]
  • Metwaly G., Wu Y., Peplowska K., Röhrl J., Soh Y.-M., Bürmann F., Gruber S., Storchova Z.*, 2020. Phospho-regulation of the Shugoshin-Condensin interaction at the centromere in budding yeast.
    PLOS Genetics
    16(8) [Pubmed] [DOI]
    preprint [BioRxiv]
  • Jeon J.-H., Lee H.-S., Shin H.-C., Kwak M.-J., Kim Y.-G., Gruber S. and Oh B.-H.*, 2020. Evidence for binary Smc complexes lacking kite subunits in archaea.
    IUCrJ
    7(2) [Pubmed] [DOI]
  • Prassler J., Simon F., Ecke M., Gruber S. and Gerisch G.* 2020. Decision making in phagocytosis.
    AEMB
    1246:71-81 [Pubmed] [DOI] [PDF]

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] [Free] [PDB: 6SDK] [PDF] [F1000_recommendations] [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] [Free full-text] [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) p. 2003-2016 [DOI[Web of Science[Pubmed]
  • Haering C. H., Gruber S., 2016. SnapShot: SMC Protein Complexes Part I.
    Cell
    164(1-2) p. 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) p. 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) p. 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) p. 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) p. e00662 [DOI[Web of Science[Pubmed]
  • Bürmann F., Gruber S., 2015. SMC condensin: promoting cohesion of replicon arms.
    Nature Structural & Molecular Biology
    22(9) p. 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) p. 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) p. 963-967 [DOI[Web of Science[Pubmed]
  • Gruber S., 2014. Multilayer chromosome organization through DNA bending, bridging and extrusion.
    Current Opinion In Microbiology
    22 p. 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) p. 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) p. 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) p. 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) p. 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) p. 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) p. 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) p. 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) p. 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) p. 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) p. 727-739 [DOI] [Web of Science[Pubmed]