A5029239320- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Cellular transport and secretion
- DNA Repair Mechanisms
- Ubiquitin and proteasome pathways
- Cellular Mechanics and Interactions
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Photosynthetic Processes and Mechanisms
- CAR-T cell therapy research
- Wnt/β-catenin signaling in development and cancer
- Nuclear Structure and Function
- Peptidase Inhibition and Analysis
- Protein Degradation and Inhibitors
- Kruppel-like factors research
- Cardiomyopathy and Myosin Studies
- DNA and Nucleic Acid Chemistry
- Protist diversity and phylogeny
- Cancer-related Molecular Pathways
- Signaling Pathways in Disease
- Plant Molecular Biology Research
- Endoplasmic Reticulum Stress and Disease
Danish Cancer Society
2019-2025
Medizinische Hochschule Hannover
2018
Article13 June 2022Open Access Source DataTransparent process Chemogenetic profiling reveals PP2A-independent cytotoxicity of proposed PP2A activators iHAP1 and DT-061 Gianmatteo Vit orcid.org/0000-0002-3111-0769 Novo Nordisk Foundation Center for Protein Research, Faculty Health Medical Sciences, University Copenhagen, Denmark Contribution: Conceptualization, Formal analysis, Supervision, Funding acquisition, Validation, Investigation, Visualization, Methodology, Writing - original draft,...
Accurate chromosome segregation in mitosis depends on multiprotein structures called kinetochores that are built the centromeric region of sister chromatids and serve to capture mitotic spindle microtubules. In early mitosis, unattached expand a crescent-shaped structure fibrous corona whose function is facilitate initial kinetochore-microtubule attachments transport by Subsequently, must be timely disassembled prevent errors. Although recent studies provided new insights molecular content...
Incorrect kinetochore–microtubule attachments during mitosis can lead to chromosomal instability, a hallmark of human cancers. Mitotic error correction relies on the kinesin-13 MCAK, microtubule depolymerase whose activity in vitro is suppressed by α-tubulin detyrosination—a posttranslational modification enriched long-lived microtubules. However, whether and how MCAK required for mitotic regulated detyrosination remains unknown. Here we found that detyrosinated accumulates correct, more...
To initiate directed movement, cells must become polarized, establishing a protrusive leading edge and contractile trailing edge. This symmetry-breaking process involves reorganization of cytoskeleton asymmetric distribution regulatory molecules. However, what triggers maintains this asymmetry during cell migration remains largely elusive. Here, we established micropatterning-based 1D motility assay to investigate the molecular basis symmetry breaking required for migration. We show that...
Abstract During cytokinesis in human cells, a failure to resolve persistent DNA bridges that span the cell-division plane maintains Aurora B-dependent abscission checkpoint an active state. However, molecular mechanism by which unresolved sister-chromatid bridging signals this is poorly defined. Here, we define essential role for Bloom’s syndrome helicase, BLM, signaling abscission-checkpoint machinery response replication stress through conversion of dsDNA into RPA-coated ssDNA. RPA then...
SiR-DNA/SiR-Hoechst is a far-red fluorescent DNA probe that routinely used for live-cell imaging of cell nuclei in interphase and chromosomes during mitosis. Despite being reported to induce damage, SiR-DNA has been more than 300 research articles, covering topics like mitosis, chromatin biology, cancer research, cytoskeletal damage response. Here, we perform comprehensive analysis the effects on mitosis four human lines (RPE-1, DLD-1, HeLa, U2OS). We report dose-, time-, light-dependent...
Abstract AMBRA1 is a crucial factor for nervous system development, and its function has been mainly associated with autophagy. It also linked to cell proliferation control, through ability regulate c-Myc D-type cyclins protein levels, thus regulating G1-S transition. However, it remains still unknown whether differentially regulated during the cycle, if this pro-autophagy exerts direct role in controlling mitosis too. Here we show that phosphorylated on multiple sites by CDK1 PLK1, two...
Microtubule-targeting agents (MTAs) have been used for decades to treat different hematologic and solid cancers. The mode of action these drugs mainly relies on their ability bind tubulin subunits and/or microtubules interfere with microtubule dynamics. In addition its MTH1-inhibiting activity, TH588 has recently identified as an MTA, whose anticancer properties were shown largely depend microtubule-targeting ability. Although inhibited polymerization in vitro reduced plus-end mobility...
Continuous poleward motion of microtubules in metazoan mitotic spindles has been fascinating generations cell biologists over the last several decades. In human cells, this so-called flux was recently shown to be driven by coordinated action four kinesins. The sliding activities kinesin-5/EG5 and kinesin-12/KIF15 are sequentially supported kinesin-7/CENP-E at kinetochores kinesin-4/KIF4A on chromosome arms, with individual contributions peaking during prometaphase metaphase, respectively....
Abstract Mitotic spindle microtubules (MTs) undergo continuous poleward flux, whose driving force and function in humans remain unclear. Here, we combined loss-of-function screenings with analysis of MT dynamics human cells to investigate the molecular mechanisms underlying MT-flux. We report that kinesin-7/CENP-E at kinetochores (KTs) is predominant driver MT-flux early prometaphase, while kinesin-4/KIF4A on chromosome arms facilitates during late prometaphase metaphase. show both these...
Abstract PP2A is an abundant phosphoprotein phosphatase that acts as a tumor suppressor. For this reason, compounds able to activate are attractive anticancer agents. The small molecule iHAP1 and DT-061 have recently been reported by Leonard et al. (2020) Morita in Cell selectively stabilize specific PP2A-B56 complexes which mediate cell killing. Here, we show not the case question key findings these papers. Through genome wide CRISPR-Cas9 screens, uncover biological pathways targeted...
To initiate directed movement, cells must become polarized, establishing a protrusive leading edge and contractile trailing edge. This symmetry-breaking process involves reorganization of cytoskeleton asymmetric distribution regulatory molecules. However, what triggers maintains this asymmetry during cell migration remains largely elusive. Here, we established micropatterning-based 1D motility assay to investigate the molecular basis required for migration. We show that microtubule...
Abstract Accurate chromosome segregation in mitosis depends on multiprotein structures called kinetochores (KTs) that are built the centromeric region of sister chromatids and serve to capture mitotic spindle microtubules (MTs). In early mitosis, unattached KTs expand a crescent-shaped structure fibrous corona whose function is facilitate initial KT-MT attachments transport by MTs. Subsequently, must be timely disassembled prevent errors. Although recent studies provided new insights...
Abstract Incorrect kinetochore-microtubule attachments during mitosis can lead to chromosomal instability, a hallmark of human cancers. Mitotic error correction relies on the kinesin-13 MCAK, microtubule depolymerase whose activity in vitro is suppressed by α-tubulin detyrosination - post-translational modification enriched long-lived microtubules. However, whether and how MCAK required for mitotic regulated tyrosination/detyrosination remains unknown. Here we found that accumulates correct,...