ZMB Member Stefan Westermann

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Prof. Dr. Stefan Westermann

Phone
+49 201 183 2733
Email

Fakultät für Biologie
Room S05 R01 H75
Universität Duisburg-Essen
45117 Essen

Department

Molecular Genetics I

Research Overview

Kinetochores and the Microtubule Cytoskeleton

Starting out from a single fertilized egg, an adult human body contains about 100 Trillion cells. All of the cells in an organism are generated by division of existing cells, and the genomic building plan of the organism, in the form of chromosomes, needs to be exactly copied and divided between cells during the division process. How do cells achieve the segregation of their genomes with such remarkable precision? What type of molecular defects may underlie errors in chromosome segregation, which can give rise to birth defects and cancer? My laboratory is trying to understand how the duplicated genome is passed accurately from one cell generation to the next. We are following two related questions:

  1. How are Kinetochores constructed to allow accurate chromosome segregation? We are performing a detailed functional analysis and biochemical reconstitution of the budding yeast kinetochore.
  2. How are Microtubules organized and regulated to move chromosomes? We are investigating molecular motors and other microtubule-associated proteins in order to understand how they function, how they are regulated and how they organize microtubules.

Experimental Techniques

  • In-vitro reconstitution and biochemical analysis of proteins and multi-protein complexes.
  • Yeast genetics and functional analysis of the chromosome segregation machinery in-vivo.
  • Advanced imaging techniques, such as total internal reflection fluorescence microscopy with single-molecule sensitivity and reconstituted assays for dynamic microtubule growth.
Read more

    Journal articles

  • Killinger, Kerstin; Böhm, Miriam; Steinbach, Philine; Hagemann, Götz; Blüggel, Mike; Jänen, Karolin; Hohoff, Simone; Bayer, Peter; Herzog, Franz; Westermann, Stefan
    Auto-inhibition of Mif2/CENP-C ensures centromere-dependent kinetochore assembly in budding yeast
    In: The EMBO Journal (2020) pp. e102938
    ISSN: 1460-2075; 0261-4189
  • Schmitzberger, Florian; Richter, Magdalena M; Gordiyenko, Yuliya; Robinson, Carol V; Dadlez, Michał; Westermann, Stefan
    Molecular basis for inner kinetochore configuration through RWD domain–peptide interactions
    In: The EMBO Journal Vol. 36 (2017) Nr. 23, pp. 3458 - 3482
    ISSN: 1460-2075; 0261-4189
  • Howes, Stuart C.; Geyer, Elisabeth A.; LaFrance, Benjamin; Zhang, Rui; Kellogg, Elizabeth H.; Westermann, Stefan; Rice, Luke M.; Nogales, Eva
    Structural differences between yeast and mammalian microtubules revealed by cryo-EM
    In: The Journal of Cell Biology (JCB) Vol. 216 (2017) Nr. 9, pp. 2669 - 2677
    ISSN: 1540-8140; 0021-9525
  • van der Vaart, Babet; Fischböck, Josef; Mieck, Christine; Pichler, Peter; Mechtler, Karl; Medema, René H.; Westermann, Stefan
    TORC1 signaling exerts spatial control over microtubule dynamics by promoting nuclear export of Stu2
    In: The Journal of Cell Biology (JCB) Vol. 216 (2017) Nr. 11, pp. 3471 - 3484
    ISSN: 1540-8140; 0021-9525
  • Molodtsov, Maxim I.; Mieck, Christine; Dobbelaere, Jeroen; Dammermann, Alexander; Westermann, Stefan; Vaziri, Alipasha
    A Force-Induced Directional Switch of a Molecular Motor Enables Parallel Microtubule Bundle Formation
    In: Cell Vol. 167 (2016) Nr. 2, pp. 539 - 552.e14
    ISSN: 1097-4172; 0092-8674
  • Weissmann, Florian; Peters, Jan-Michael; Schulman, Brenda A.; Westermann, Stefan; Lampert, Fabienne; Stark, Holger; Huis in 't Veld, Pim J.; VanderLinden, Ryan; Petzold, Georg
    BiGBac enables rapid gene assembly for the expression of large multisubunit protein complexes
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 113 (2016) Nr. 19, pp. E2564 - E2569
    ISSN: 1091-6490; 0027-8424
  • Pekgöz Altunkaya, Gülsah; Malvezzi, Francesca; Demianova, Zuzana; Zimniak, Tomasz; Litos, Gabriele; Weissmann, Florian; Mechtler, Karl; Herzog, Franz; Westermann, Stefan
    CCAN Assembly Configures Composite Binding Interfaces to Promote Cross-Linking of Ndc80 Complexes at the Kinetochore
    In: Current Biology Vol. 26 (2016) Nr. 17, pp. 2370 - 2378
    ISSN: 1879-0445
  • Mieck, Christine; Molodtsov, Maxim I.; Drzewicka, Katarzyna; van der Vaart, Babet; Litos, Gabriele; Schmauss, Gerald; Vaziri, Alipasha; Westermann, Stefan
    Non-catalytic motor domains enable processive movement and functional diversification of the kinesin-14 Kar3
    In: eLife Vol. 4 (2015) pp. e04489
    ISSN: 2050-084X
  • Hornung, Peter; Troc, Paulina; Malvezzi, Francesca; Maier, Michael; Demianova, Zuzana; Zimniak, Tomasz; Litos, Gabriele; Lampert, Fabienne; Schleiffer, Alexander; Brunner, Matthias; Mechtler, Karl; Herzog, Franz; Marlovits, Thomas C.; Westermann, Stefan
    A cooperative mechanism drives budding yeast kinetochore assembly downstream of CENP-A
    In: The Journal of Cell Biology (JCB) Vol. 206 (2014) Nr. 4, pp. 506 - 524
    ISSN: 0021-9525; 1540-8140
  • Malvezzi, Francesca; Westermann, Stefan
    “Uno, nessuno e centomila” : the different faces of the budding yeast kinetochore
    In: Chromosoma Vol. 123 (2014) Nr. 5, pp. 447 - 457
    ISSN: 1432-0886; 0009-5915
  • Malvezzi, Francesca; Litos, Gabriele; Schleiffer, Alexander; Heuck, Alexander; Mechtler, Karl; Clausen, Tim; Westermann, Stefan
    A structural basis for kinetochore recruitment of the Ndc80 complex via two distinct centromere receptors
    In: The EMBO Journal Vol. 32 (2013) Nr. 3, pp. 409 - 423
    ISSN: 1460-2075
  • Earnshaw, William C.; Allshire, Robin C.; Black, Ben E.; Bloom, Kerry; Brinkley, Bill R.; Brown, William; Cheeseman, Iain M.; Choo, Kong H. A.; Copenhaver, Gregory P.; DeLuca, Jennifer G.; Desai, Arshad; Diekmann, Stephan; Erhardt, Sylvia; Fitzgerald-Hayes, Molly; Foltz, Daniel; Fukagawa, Tatsuo; Gassmann, Reto; Gerlich, Daniel W.; Glover, David M.; Gorbsky, Gary J.; Harrison, Stephen C.; Heun, Patrick; Hirota, Toru; Jansen, Lars E. T.; Karpen, Gary; Kops, Geert J. P. L.; Lampson, Michael A.; Lens, Susanne M.; Losada, Ana; Luger, Karolin; Maiato, Helder; Maddox, Paul S.; Margolis, Robert L.; Masumoto, Hiroshi; McAinsh, Andrew D.; Mellone, Barbara G.; Meraldi, Patrick; Musacchio, Andrea; Oegema, Karen; O'Neill, Rachel J.; Salmon, Edward D.; Scott, Kristin C.; Straight, Aaron F.; Stukenberg, Peter T.; Sullivan, Beth A.; Sullivan, Kevin F.; Sunkel, Claudio E.; Swedlow, Jason R.; Walczak, Claire E.; Warburton, Peter E.; Westermann, Stefan; Willard, Huntington F.; Wordeman, Linda; Yanagida, Mitsuhiro; Yen, Tim J.; Yoda, Kinya; Cleveland, Don W.
    Esperanto for histones : CENP-A, not CenH3, is the centromeric histone H3 variant
    In: Chromosome Research Vol. 21 (2013) Nr. 2, pp. 101 - 106
    ISSN: 0967-3849; 1573-6849
  • Lampert, Fabienne; Mieck, Christine; Alushin, Gregory M.; Nogales, Eva; Westermann, Stefan
    Molecular requirements for the formation of a kinetochore–microtubule interface by Dam1 and Ndc80 complexes
    In: The Journal of Cell Biology (JCB) Vol. 200 (2013) Nr. 1, pp. 21 - 30
    ISSN: 0021-9525
  • Schleiffer, Alexander; Maier, Michael; Litos, Gabriele; Lampert, Fabienne; Hornung, Peter; Mechtler, Karl; Westermann, Stefan
    CENP-T proteins are conserved centromere receptors of the Ndc80 complex
    In: Nature Cell Biology Vol. 14 (2012) Nr. 6, pp. 604 - 613
    ISSN: 1476-4679; 1097-6256
  • Westermann, Stefan; Schleiffer, Alexander
    Family matters: structural and functional conservation of centromere-associated proteins from yeast to humans
    In: Trends in Cell Biology Vol. 23 (2012) Nr. 6, pp. 260 - 269
    ISSN: 1879-3088; 0962-8924
  • Zimniak, Tomasz; Fitz, Veronika; Zhou, Hongwen; Lampert, Fabienne; Opravil, Susanne; Mechtler, Karl; Stolt-Bergner, Peggy; Westermann, Stefan
    Spatiotemporal regulation of Ipl1/Aurora activity by direct Cdk1 phosphorylation
    In: Current Biology Vol. 22 (2012) Nr. 9, pp. 787 - 793
    ISSN: 1879-0445
  • Lampert, Fabienne; Westermann, Stefan
    A blueprint for kinetochores - new insights into the molecular mechanics of cell division
    In: Nature reviews. Molecular cell biology Vol. 12 (2011) Nr. 7, pp. 407 - 412
    ISSN: 1471-0080
  • Hornung, Peter; Maier, Michael; Alushin, Gregory M.; Lander, Gabriel C.; Nogales, Eva; Westermann, Stefan
    Molecular architecture and connectivity of the budding yeast Mtw1 kinetochore complex
    In: Journal of Molecular Biology Vol. 405 (2011) Nr. 2, pp. 548 - 559
    ISSN: 0022-2836; 1089-8638
  • Lampert, Fabienne; Hornung, Peter; Westermann, Stefan
    The Dam1 complex confers microtubule plus end–tracking activity to the Ndc80 kinetochore complex
    In: The Journal of Cell Biology (JCB) Vol. 189 (2010) Nr. 4, pp. 641 - 649
    ISSN: 0021-9525
  • Kiermaier, Eva; Woehrer, Sophie; Peng, Yutian; Mechtler, Karl; Westermann, Stefan
    A Dam1-based artificial kinetochore is sufficient to promote chromosome segregation in budding yeast
    In: Nature Cell Biology Vol. 11 (2009) Nr. 9, pp. 1109 - 1115
    ISSN: 1476-4679; 1097-6256
  • Zimniak, Tomasz; Stengl, Katharina; Mechtler, Karl; Westermann, Stefan
    Phosphoregulation of the budding yeast EB1 homologue Bim1p by Aurora/Ipl1p
    In: The Journal of Cell Biology (JCB) Vol. 186 (2009) Nr. 3, pp. 379 - 391
    ISSN: 0021-9525
  • Wang, Hong-Wei; Long, Sydney; Ciferri, Claudio; Westermann, Stefan; Drubin, David G.; Barnes, Georjana; Nogales, Eva
    Architecture and flexibility of the yeast Ndc80 kinetochore complex
    In: Journal of Molecular Biology Vol. 383 (2008) Nr. 4, pp. 894 - 903
    ISSN: 0022-2836; 1089-8638
  • Grishchuk, Ekaterina L.; Spiridonov, Ilia S.; Volkov, Vladimir A.; Efremov, Artem K.; Westermann, Stefan; Drubin, David G.; Barnes, Georjana; Ataullakhanov, Fazly I.; McIntosh, J. Richard
    Different assemblies of the DAM1 complex follow shortening microtubules by distinct mechanisms
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 105 (2008) Nr. 19, pp. 6918 - 6923
    ISSN: 1091-6490; 0027-8424
  • Grishchuk, Ekaterina L.; Efremov, Artem K.; Volkov, Vladimir A.; Spiridonov, Ilia S.; Gudimchuk, Nikita; Westermann, Stefan; Drubin, David G.; Barnes, Georjana; McIntosh, J. Richard; Ataullakhanov, Fazly I.
    The Dam1 ring binds microtubules strongly enough to be a processive as well as energy-efficient coupler for chromosome motion
    In: Proceedings of the National Academy of Sciences of the United States of America (PNAS) Vol. 105 (2008) Nr. 40, pp. 15423 - 15428
    ISSN: 1091-6490; 0027-8424
  • Wong, Jonathan; Nakajima, Yuko; Westermann, Stefan; Shang, Ching; Kang, Jung-seog; Goodner, Crystal; Houshmand, Pantea; Fields, Stanley; Chan, Clarence S. M.; Drubin, David G.; Barnes, Georjana; Hazbun, Tony
    A protein interaction map of the mitotic spindle
    In: Molecular Biology of the Cell (MBoC) Vol. 18 (2007) Nr. 10, pp. 3800 - 3809
    ISSN: 1939-4586
  • Wang, Hong-Wei; Ramey, Vincent H.; Westermann, Stefan; Leschziner, Andres E.; Welburn, Julie P. I.; Nakajima, Yuko; Drubin, David G.; Barnes, Georjana; Nogales, Eva
    Architecture of the Dam1 kinetochore ring complex and implications for microtubule-driven assembly and force-coupling mechanisms
    In: Nature structural & molecular biology Vol. 14 (2007) Nr. 8, pp. 721 - 726
    ISSN: 1545-9985; 1545-9993
  • Westermann, Stefan; Drubin, David G.; Barnes, Georjana
    Structures and functions of yeast kinetochore complexes
    In: Annual Review of Biochemistry Vol. 76 (2007) pp. 563 - 591
    ISSN: 1545-4509
  • Westermann, Stefan; Wang, Hong-Wei; Avila-Sakar, Augustin; Drubin, David G.; Nogales, Eva; Barnes, Georjana
    The Dam1 kinetochore ring complex moves processively on depolymerizing microtubule ends
    In: Nature Vol. 440 (2006) Nr. 7083, pp. 565 - 569
    ISSN: 0028-0836; 1476-4687
  • Westermann, Stefan; Avila-Sakar, Augustin; Wang, Hong-Wei; Niederstrasser, Hanspeter; Wong, Jonathan; Drubin, David G.; Nogales, Eva; Barnes, Georjana
    Formation of a dynamic kinetochore-microtubule interface through assembly of the Dam1 ring complex
    In: Molecular Cell Vol. 17 (2005) Nr. 2, pp. 277 - 290
    ISSN: 1097-2765
  • Westermann, Stefan; Cheeseman, Iain M.; Anderson, Scott; Yates, John R.; Drubin, David G.; Barnes, Georjana
    Architecture of the budding yeast kinetochore reveals a conserved molecular core
    In: The Journal of Cell Biology (JCB) Vol. 163 (2003) Nr. 2, pp. 215 - 222
    ISSN: 0021-9525

ZMB Research Programme

Prof.Stefan Westermann participates in the ZMB research programme III, Molecular and Chemical Cell Biology.