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MolStruKT SIGNED

Molecular structure and cell cycle regulated assembly of the kinetochore

Total Cost €

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EC-Contrib. €

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Partnership

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 MolStruKT project word cloud

Explore the words cloud of the MolStruKT project. It provides you a very rough idea of what is the project "MolStruKT" about.

missing    centromere    distance    budding    functional    protein    minichromosomes    stable    exit    separation    assembled    fidelity    soluble    propagation    mechanistic    mass    insights    stoichiometries    chromatid    sensing    mitosis    chromosomes    time    topological    tension    combined    replenishment    reveal    cross    first    structure    generations    yeast    levels    bind    directing    dynamic    subunit    sister    chromosome    significantly    tumorigenesis    chromosomal    kinetochore    assembling    architecture    function    structures    attach    tight    phosphorylation    eukaryotes    feedback    nucleosome    characterizing    secondly    microtubules    network    segregation    crystallography    spectrometry    passenger    fundamental    aneuploidy    molecular    systematic    mitotic    analyze    thirdly    kinetochores    temporal    cxms    complexes    defects    macromolecular    confers    spindle    identity    assembly    centromeres    chemical    human    native    accurate    ray    linking    proteins    unveil    subcomplexes    restraints    understand    elucidate    cenp   

Project "MolStruKT" data sheet

The following table provides information about the project.

Coordinator
LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN 

Organization address
address: GESCHWISTER SCHOLL PLATZ 1
city: MUENCHEN
postcode: 80539
website: www.uni-muenchen.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website https://www.genzentrum.uni-muenchen.de/research-groups/herzog/index.html
 Total cost 1˙499˙932 €
 EC max contribution 1˙499˙932 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-06-01   to  2020-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN DE (MUENCHEN) coordinator 1˙499˙932.00

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 Project objective

Accurate chromosome segregation in eukaryotes requires the assembly of the macromolecular kinetochore complex at centromeres to attach chromosomes to the mitotic spindle. The kinetochore proteins are organized in stable subcomplexes that bind to dynamic microtubules and ensure fidelity of sister chromatid separation through feedback control. Characterizing the kinetochore structure will significantly advance our understanding of chromosome segregation and how defects in this process can lead to aneuploidy, which is associated with tumorigenesis. X-ray crystallography has provided detailed insights into the function of subcomplexes, however, a molecular analysis of the native kinetochore subunit architecture is still missing. I have recently combined chemical cross-linking with mass spectrometry (CXMS) which allows for the first time the topological analysis of native macromolecular protein structures by a comprehensive set of distance restraints. Applying this approach to kinetochores assembled on budding yeast minichromosomes I aim to elucidate the architecture of the native centromere-assembled kinetochore complex and analyze how tension sensing by the chromosomal passenger complex is integrated into the structure. Secondly, the systematic analyses of changes in phosphorylation levels and in protein stoichiometries of soluble and nucleosome-associated human kinetochore complexes will reveal how the tight temporal control of assembling a functional kinetochore in mitosis is achieved. Thirdly, I will investigate the architecture of the centromere-associated network of kinetochore proteins by CXMS to unveil its role in directing CENP-A replenishment at mitotic exit in order to maintain centromere identity through generations. The analysis of the native kinetochore structure in different functional states will provide fundamental mechanistic insights and help us to understand how this architecture confers fidelity to centromere propagation and chromosome segregation.

 Publications

year authors and title journal last update
List of publications.
2019 Josef Fischböck-Halwachs, Sylvia Singh, Mia Potocnjak, Götz Hagemann, Victor Solis-Mezarino, Stephan Woike, Medini Ghodgaonkar-Steger, Florian Weissmann, Laura D Gallego, Julie Rojas, Jessica Andreani, Alwin Köhler, Franz Herzog
The COMA complex interacts with Cse4 and positions Sli15/Ipl1 at the budding yeast inner kinetochore
published pages: , ISSN: 2050-084X, DOI: 10.7554/elife.42879
eLife 8 2020-03-10
2017 Shyamal Mosalaganti, Jenny Keller, Anika Altenfeld, Michael Winzker, Pascaline Rombaut, Michael Saur, Arsen Petrovic, Annemarie Wehenkel, Sabine Wohlgemuth, Franziska Müller, Stefano Maffini, Tanja Bange, Franz Herzog, Herbert Waldmann, Stefan Raunser, Andrea Musacchio
Structure of the RZZ complex and molecular basis of its interaction with Spindly
published pages: 961-981, ISSN: 0021-9525, DOI: 10.1083/jcb.201611060
The Journal of Cell Biology 216/4 2019-04-18
2016 Alexander Heuck, Sonja Schitter-Sollner, Marcin Józef Suskiewicz, Robert Kurzbauer, Juliane Kley, Alexander Schleiffer, Pascaline Rombaut, Franz Herzog, Tim Clausen
Structural basis for the disaggregase activity and regulation of Hsp104
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.21516
eLife 5 2019-04-18
2016 Seychelle M Vos, David Pöllmann, Livia Caizzi, Katharina B Hofmann, Pascaline Rombaut, Tomasz Zimniak, Franz Herzog, Patrick Cramer
Architecture and RNA binding of the human negative elongation factor
published pages: , ISSN: 2050-084X, DOI: 10.7554/eLife.14981
eLife 5 2019-04-18
2016 Elisabeth Schmidtmann, Tobias Anton, Pascaline Rombaut, Franz Herzog, Heinrich Leonhardt
Determination of local chromatin composition by CasID
published pages: 476-484, ISSN: 1949-1034, DOI: 10.1080/19491034.2016.1239000
Nucleus 7/5 2019-04-18
2017 Victor Solis-Mezarino, Franz Herzog
compleXView: a server for the interpretation of protein abundance and connectivity information to identify protein complexes
published pages: W276-W284, ISSN: 0305-1048, DOI: 10.1093/nar/gkx411
Nucleic Acids Research 45/W1 2019-04-18
2016 Herzog, Franz; Jenni, Simon; Rombaut, Pascaline; Musacchio, Andrea; Overlack, Katharina; van Gerwen, Suzan; Stege, Patricia; Vetter, Ingrid; Wohlgemuth, Sabine; Dimitrova, Yoana N.; Harrison, Stephen C.; John, Juliane; Petrovic, Arsen; Keller, Jenny; Liu, Yahui
Structure of the MIS12 Complex and Molecular Basis of Its Interaction with CENP-C at Human Kinetochores
published pages: 1028–1040.e15, ISSN: 0092-8674, DOI: 10.1016/j.cell.2016.10.005
Cell 167/4 2019-05-27
2016 John R. Weir, Alex C. Faesen, Kerstin Klare, Arsen Petrovic, Federica Basilico, Josef Fischböck, Satyakrishna Pentakota, Jenny Keller, Marion E. Pesenti, Dongqing Pan, Doro Vogt, Sabine Wohlgemuth, Franz Herzog, Andrea Musacchio
Insights from biochemical reconstitution into the architecture of human kinetochores
published pages: 249-253, ISSN: 0028-0836, DOI: 10.1038/nature19333
Nature 537/7619 2019-05-27
2016 Petrovic, Arsen; Musacchio, Andrea; Liu, Yahui; Keller, Jenny; Rombaut, Pascaline; Mosalaganti, Shyamal; Herzog, Franz; Raunser, Stefan
Insights from the reconstitution of the divergent outer kinetochore of Drosophila melanogaster
published pages: , ISSN: 2046-2441, DOI: 10.1098/rsob.150236
Open Biology 2 2019-05-27

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