A5055191083- Genomics and Chromatin Dynamics
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
- RNA and protein synthesis mechanisms
- Plant Molecular Biology Research
- DNA and Nucleic Acid Chemistry
- Photosynthetic Processes and Mechanisms
- Epigenetics and DNA Methylation
- Cellular transport and secretion
- CRISPR and Genetic Engineering
- Glycosylation and Glycoproteins Research
- Cancer-related Molecular Pathways
- Advanced Proteomics Techniques and Applications
- Protein Structure and Dynamics
- Protein Degradation and Inhibitors
- Endoplasmic Reticulum Stress and Disease
- Plant nutrient uptake and metabolism
- Hippo pathway signaling and YAP/TAZ
- Mass Spectrometry Techniques and Applications
- Cancer Genomics and Diagnostics
- Enzyme Structure and Function
- Autophagy in Disease and Therapy
Research Institute of Molecular Pathology
2016-2025
Vienna Biocenter
2016-2025
Medical University of Vienna
2019-2020
Stanford University
2019
Österreichisches Forschungsinstitut für Chemie und Technik
2012
Max Planck Society
2010
Institute of Molecular Biotechnology
2009-2010
Wienerberger (Czechia)
2010
Max Planck Institute for Biophysical Chemistry
2009
European Molecular Biology Laboratory
2009
The proper segregation of sister chromatids in mitosis depends on bipolar attachment all chromosomes to the mitotic spindle. We have identified small molecule Hesperadin as an inhibitor chromosome alignment and segregation. Our data imply that causes this phenotype by inhibiting function kinase Aurora B. Mammalian cells treated with enter anaphase presence numerous monooriented chromosomes, many which may both kinetochores attached one spindle pole (syntelic attachment). also arrested taxol...
Cyclin B is degraded at the onset of anaphase by a ubiquitin-dependent proteolytic system. We have fractionated mitotic Xenopus egg extracts to identify components required for this process. find that UBC4 and least one other ubiquitin-conjugating enzyme can support cyclin ubiquitination. The specificity ubiquitination determined 20S complex contains homologs budding yeast CDC16 CDC27. Because these proteins are in mammalian cells, we refer as anaphase-promoting (APC). CDC27 antibodies...
O Cohen-Fix, J M Peters, W Kirschner, and D Koshland Department of Embryology, Carnegie Institution Washington, Baltimore, Maryland 21210, USA.
Eukaryotic genomes are folded into loops and topologically associating domains, which contribute to chromatin structure, gene regulation, recombination. These structures depend on cohesin, a ring-shaped DNA-entrapping adenosine triphosphatase (ATPase) complex that has been proposed form by extrusion. Such an activity observed for condensin, forms in mitosis, but not cohesin. Using biochemical reconstitution, we found single human cohesin complexes DNA symmetrically at rates up 2.1 kilo-base...
Cell division depends on the separation of sister chromatids in anaphase. In yeast, is initiated by cleavage cohesin protease separase. vertebrates, most removed from chromosome arms a cleavage-independent mechanism. Only residual amounts are cleaved at onset anaphase, coinciding with its disappearance centromeres. We have identified two separase sites human subunit SCC1 and conditionally expressed noncleavable mutants cells. Our results indicate that essential for chromatid completion cytokinesis.
Chromosome segregation and cell division are essential, highly ordered processes that depend on numerous protein complexes. Results from recent RNA interference screens indicate the identity composition of these complexes is incompletely understood. Using gene tagging bacterial artificial chromosomes, localization, tandem-affinity purification-mass spectrometry, MitoCheck consortium has analyzed about 100 human complexes, many which had not or only been characterized. This work led to...
The ordered activation of the ubiquitin protein ligase anaphase-promoting complex (APC) or cyclosome by CDC20 in metaphase and CDH1 telophase is essential for anaphase exit from mitosis, respectively. Here, we show that can only bind to activate mitotically phosphorylated form Xenopus human APC vitro. In contrast, analysis nonphosphorylated forms suggests phosphorylation neither sufficient nor required activation. On basis these results observation correlates with vivo, propose mitotic an...
Cohesin is a protein complex that required to hold sister chromatids together. Cleavage of the Scc1 subunit cohesin by protease separase releases from chromosomes and thereby enables separation in anaphase. In vertebrate cells, bulk dissociates chromosome arms already during prophase prometaphase without cleavage Scc1. Polo-like kinase 1 (Plk1) Aurora-B are for this dissociation process, Plk1 can phosphorylate subunits SA2 vitro, consistent with possibility phosphorylation triggers arms....
Cyclin A is a stable protein in S and G2 phases, but destabilized when cells enter mitosis almost completely degraded before the metaphase to anaphase transition. Microinjection of antibodies against subunits anaphase-promoting complex/cyclosome (APC/C) or human Cdc20 (fizzy) arrested at stabilized both cyclins B1. was efficiently polyubiquitylated by Cdh1-activated APC/C vitro, contrast cyclin B1, proteolysis not delayed spindle assembly checkpoint. The degradation B1 accelerated inhibition...
In eukaryotes, sister chromatids remain connected from the time of their synthesis until they are separated in anaphase. This cohesion depends on a complex proteins called cohesins. budding yeast, anaphase-promoting (APC) pathway initiates anaphase by removing cohesins chromosomes. vertebrates, dissociate chromosomes already prophase. To study mitotic regulation we have purified two 14S cohesin complexes human cells. Both contain SMC1, SMC3, SCC1, and either one yeast Scc3p orthologs SA1...