A5044856730- Microtubule and mitosis dynamics
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Cancer Genomics and Diagnostics
- Genomics and Chromatin Dynamics
- Prion Diseases and Protein Misfolding
- DNA Repair Mechanisms
- Fungal and yeast genetics research
- Cancer Research and Treatments
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- RNA Research and Splicing
- Prenatal Screening and Diagnostics
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- Bacteriophages and microbial interactions
- Heat shock proteins research
- RNA modifications and cancer
- Autophagy in Disease and Therapy
- Genomics and Phylogenetic Studies
- CRISPR and Genetic Engineering
- Virus-based gene therapy research
- Genetic and Kidney Cyst Diseases
- RNA Interference and Gene Delivery
University of Kaiserslautern
2016-2024
Rheinland-Pfälzische Technische Universität Kaiserslautern-Landau
2023-2024
Max Planck Institute of Biochemistry
2011-2021
Max Planck Society
2008-2019
Ludwig-Maximilians-Universität München
2014-2018
Center for Integrated Protein Science Munich
2013-2016
Gold Skin Care Center
2015
Harvard University
2004-2011
Charles University
1997-2010
Dana-Farber Cancer Institute
2003-2007
Do young and old protein molecules have the same probability to be degraded? We addressed this question using metabolic pulse-chase labeling quantitative mass spectrometry obtain degradation profiles for thousands of proteins. find that >10% proteins are degraded non-exponentially. Specifically, less stable in first few hours their life stabilize with age. Degradation conserved similar two cell types. Many non-exponentially (NED) subunits complexes produced super-stoichiometric amounts...
Abstract Aneuploidy is a hallmark of cancer and underlies genetic disorders characterized by severe developmental defects, yet the molecular mechanisms explaining its effects on cellular physiology remain elusive. Here we show, using series human cells with defined aneuploid karyotypes, that gain single chromosome increases genomic instability. Next-generation sequencing SNP-array analysis reveal accumulation chromosomal rearrangements in aneuploids, break point junction patterns suggestive...
DNA interstrand cross-links (ICLs) block replication fork progression by inhibiting strand separation. Repair of ICLs requires sequential incisions, translesion synthesis, and homologous recombination, but the full set factors involved in these transactions remains unknown. We devised a technique called chromatin mass spectrometry (CHROMASS) to study protein recruitment dynamics during perturbed Xenopus egg extracts. Using CHROMASS, we systematically monitored assembly disassembly on...
Highlights•Single-chromosome gains inhibit anchorage-independent growth and xenograft formation•P53 loss Ras activation fail to normalize the fitness of trisomic cells•Trisomic cells acquire additional karyotype changes during prolonged growth•Trisomic can evolve over time a higher-fitness stateSummaryAneuploidy is hallmark cancer, although its effects on tumorigenesis are unclear. Here, we investigated relationship between aneuploidy cancer development using engineered harbor single extra...
Diploid and stable karyotypes are associated with health fitness in animals. By contrast, whole-genome duplications-doublings of the entire complement chromosomes-are linked to genetic instability frequently found human cancers1-3. It has been established that duplications fuel chromosome through abnormal mitosis4-8; however, immediate consequences tetraploidy first interphase not known. This is a key question because single duplication events such as cytokinesis failure can promote...
Abstract Chromosomal instability (CIN) and epigenetic alterations are characteristics of advanced metastatic cancers 1–4 , but whether they mechanistically linked is unknown. Here we show that missegregation mitotic chromosomes, their sequestration in micronuclei 5,6 subsequent rupture the micronuclear envelope 7 profoundly disrupt normal histone post-translational modifications (PTMs), a phenomenon conserved across humans mice, as well cancer non-transformed cells. Some changes PTMs occur...
Up to 80% of human cancers, in particular solid tumors, contain cells with abnormal chromosomal numbers, or aneuploidy, which is often linked marked instability. Whereas some tumors the aneuploidy occurs by missegregation one a few chromosomes, can also arise during proliferation inherently unstable tetraploid generated whole genome doubling from diploid cells. Recent findings cancer sequencing projects suggest that nearly 40% underwent at point tumorigenesis, yet its contribution phenotypes...
Cohesin plays an important role in chromatid cohesion and has additional functions higher-order chromatin organization transcriptional regulation. The binding of cohesin to euchromatic regions is largely mediated by CTCF or the mediator complex. However, it currently unknown how recruited pericentric heterochromatin mammalian cells. Here we define histone methyltransferase Suv4-20h2 as a major structural constituent that mediates compaction recruitment. stably associates with through...
Aneuploidy, a condition characterized by chromosome gains and losses, causes reduced fitness numerous cellular stresses, including increased protein aggregation. Here, we identify complex stoichiometry imbalances as major cause of aggregation in aneuploid cells. Subunits complexes encoded on excess chromosomes aggregate cells, which is suppressed when expression other subunits coordinately altered. We further show that are either degraded or nearly effective degradation at lowering levels...
Aneuploidy, a karyotype deviating from multiples of haploid chromosome set, affects the physiology eukaryotes. In humans, aneuploidy is linked to pathological defects such as developmental abnormalities, mental retardation or cancer, but underlying mechanisms remain elusive. There are many different types and origins aneuploidy, whether there uniform cellular response in human cells has not been addressed so far.Here we evaluate transcription profiles eleven trisomic tetrasomic cell lines...
Cancer cells often harbor chromosomes in abnormal numbers and with aberrant structure. The consequences of these chromosomal aberrations are difficult to study cancer, therefore several model systems have been developed recent years. We show that human extra chromosome engineered via microcell-mediated transfer gain massive rearrangements. rearrangements arose by shattering rejoining as well replication-dependent mechanisms. the isolated micronuclei lack functional lamin B1 become prone...
Most mitochondrial proteins are synthesized as precursors in the cytosol and post-translationally transported into mitochondria. The surface protein Tom70 acts at interface of In vitro import experiments identified targeting receptor, particularly for hydrophobic carriers. Using vivo methods high-content screens, we revisit question function considerably expand set Tom70-dependent proteins. We demonstrate that crucial activity is its ability to recruit cytosolic chaperones outer membrane....
Abstract Aneuploidy is a hallmark of cancer with tissue-specific prevalence patterns that suggest it plays driving role in initiation and progression. However, the contribution aneuploidy to tumorigenesis depends on both cellular genomic contexts. Whole-genome duplication (WGD) common macroevolutionary event occurs more than 30% human tumors early tumorigenesis. Although have undergone WGD are reported be permissive aneuploidy, remains unknown whether also affects patterns. Here we analyzed...