A5040403932- Microtubule and mitosis dynamics
- Chromosomal and Genetic Variations
- Cancer therapeutics and mechanisms
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- DNA and Nucleic Acid Chemistry
- Plant Genetic and Mutation Studies
- Plant Molecular Biology Research
- Lung Cancer Research Studies
- Genomic variations and chromosomal abnormalities
- Plant nutrient uptake and metabolism
- Ubiquitin and proteasome pathways
- Prion Diseases and Protein Misfolding
- Cellular transport and secretion
- Photosynthetic Processes and Mechanisms
- RNA Research and Splicing
- 14-3-3 protein interactions
- Genetic diversity and population structure
- Origins and Evolution of Life
- Endoplasmic Reticulum Stress and Disease
- Nuclear Structure and Function
- Carbohydrate Chemistry and Synthesis
- ATP Synthase and ATPases Research
- Biofield Effects and Biophysics
- Plant Reproductive Biology
Centro de Investigaciones Biológicas Margarita Salas
2000-2024
Consejo Superior de Investigaciones Científicas
1999-2024
University of Minnesota
2005-2013
University of Minnesota Medical Center
2006-2010
Twin Cities Orthopedics
2007-2010
University of Minnesota, Duluth
2005
Research Institute of Molecular Pathology
2003-2004
Vienna Biocenter
2004
Scripps Research Institute
1998-2002
Humboldt-Universität zu Berlin
1998
Metaphase chromatids are believed to consist of loops chromatin anchored a central scaffold, which major component is the decatenatory enzyme DNA topoisomerase II. Silver impregnation selectively stains an axial element metaphase and anaphase chromatids; but we find that in earlier stages mitosis, silver staining reveals initially single, folded midline structure, separates at prometaphase form two chromatid axes. Inhibition II prevents this separation, also contraction occurs when arrested....
The anaphase-promoting complex or cyclosome (APC/C) is an ubiquitin protein ligase that together with Cdc20 and Cdh1 targets mitotic proteins for degradation by the proteosome. APC–Cdc20 activity during mitosis triggers anaphase destroying securin cyclins. APC–Cdh1 promotes of cyclins other G 1 . We show loss APC/C embryogenesis early lethal before embryonic day E6.5 (E6.5). To investigate role in quiescent cells, we conditionally inactivated subunit Apc2 mice. Deletion hepatocytes caused...
The precision of the metaphase-anaphase transition ensures stable genetic inheritance. spindle checkpoint blocks anaphase onset until last chromosome biorients at metaphase plate, then bonds between sister chromatids are removed and disjoined segregate to poles. But, how separation is triggered not fully understood.We identify PIASgamma as a human E3 sumo ligase required for timely efficient chromatid separation. In cells lacking PIASgamma, normal plates form, but activated, leading...
Three species of grasshoppers have been analyzed by means a modified silver impregnation technique that reveals the presence chromatid core identifies chiasmata at first meiotic metaphase. In terms behaviour most configurations observed diplotene with orcein are easily recognized in metaphase I silver-stained bivalents. Some "hidden" configurations, as well simple chromatin associations, do not appear to represent also detected. The disposition and cores anaphase provide grounds support...
DNA topoisomerase IIα (Topo IIα) is the target of an important class anticancer drugs, but tumor cells can become resistant by reducing association enzyme with chromosomes. Here we describe a critical mechanism chromatin recruitment and exchange that relies on novel tether (ChT) domain mediates interaction histone H3 DNA. We show ChT controls residence time Topo in mitosis necessary for formation mitotic Our data suggest dynamics chromosomes are successful implicate tail posttranslational...
It has been proposed that one of the mechanisms taxane-site ligand-mediated tubulin activation is modulation structure a switch element (the M-loop) from disordered form in dimeric to folded helical microtubules. Here, we used covalent ligands, including cyclostreptin, gain further insight into this mechanism. The crystal cyclostreptin-bound reveals binding βHis229, but no stabilization M-loop. capacity cyclostreptin induce microtubule assembly compared other agents demonstrates induction...
Microtubule targeting agents (MTAs) have been exploited mainly as anti-cancer drugs because of their impact on cellular division and angiogenesis. Additionally, microtubules (MTs) are key structures for intracellular transport, which is frequently hijacked during viral infection. We analyzed the antiviral activity clinically used MTAs in infection DNA RNA viruses, including SARS-CoV-2, to find that MT destabilizer show a higher than stabilizers infections tested, FDA-approved anti-helminthic...
AbstractCheckpoint controls confer order to the cell cycle and help prevent genome instability. Here we discuss Topoisomerase II (Decatenation) Checkpoint which functions regulate mitotic progression so that chromosomes can be efficiently condensed in prophase segregated with high fidelity anaphase.
Topoisomerase II (Topo II) performs topological modifications on double-stranded DNA molecules that are essential for chromosome condensation, resolution, and segregation. In mammals, G2 metaphase cell cycle delays induced by Topo poisons have been proposed to be the result of checkpoint activation in response catenation state DNA. However, apparent lack such controls model organisms has excluded genetic proof checkpoints exist separable from conventional damage controls. But here, we define...
Abstract Key to faithful genetic inheritance is the cohesion between sister centromeres that physically links replicated chromatids and then abruptly lost at onset of anaphase. Misregulated causes aneuploidy, birth defects perhaps initiates cancers. Loss centromere controlled by spindle checkpoint thought depend on a ubiquitin ligase, Anaphase Promoting Complex/Cyclosome (APC). But here we present evidence APC pathway dispensable for separation anaphase in mammals, proceeds presence cyclin B...
AbstractClassically, chromosomal functions in DNA repair and sister chromatid association have been assigned to the cohesin proteins. More recent studies provided evidence that cohesins also localize centrosomes, which organize bipolar spindle during mitosis. Depletion of proteins is associated with multi-polar mitosis pole integrity compromised. However, defects after depletion could be an indirect consequence a cohesion defect might impact centrosome via alterations microtubule network....
Targeting microtubules is the most effective wide-spectrum pharmacological strategy in antitumoral chemotherapy, and current research focuses on reducing main drawbacks: neurotoxicity resistance. PM534 a novel synthetic compound derived from Structure-Activity-Relationship study natural molecule PM742, isolated sponge of
AbstractMulti-polar mitosis is strongly linked with aggressive cancers and it a histological diagnostic of tumor-grade. However, factors that cause chromosomes to segregate more than two spindle poles are not well understood. Here we show cohesins Rad21, Smc1 Smc3 required for bipolar in human cells. After Rad21 depletion, align at the metaphase plate spindles assemble most cases, but anaphase separated chromatids multiple poles. Time-lapse microscopy revealed often become split...
Background Proper regulation of the cohesion at centromeres human chromosomes is essential for accurate genome transmission. Exactly how maintained and then dissolved in anaphase not understood. Principal Findings We have investigated role cohesin complex cells both by depleting subunits using RNA interference also expressing a non-cleavable version Rad21 protein. depletion results aberrant anaphase, during which sister chromatids separate segregate an asynchronous fashion. However,...
The yeast separase proteins Esp1 and Cut1 are required for loss of sister chromatid cohesion that occurs at the moment anaphase onset. Circumstantial evidence has linked human to centromere separation anaphase, but a direct test role this enzyme is functionally conserved with lacking. Here we describe effects depletion from cells using RNA interference. Surprisingly, HeLa lacking delayed or arrest G2/M phase transition. This not likely due activation known checkpoint control, may be result...
Regulated separation of sister chromatids is the key event mitosis. Sister remain cohered from moment DNA duplication until anaphase. Two known factors account for cohesion: catenations and cohesin complexes. Premature loss centromeric cohesion prevented by spindle checkpoint. Here we show that sororin, a protein implicated in promoting through effects on complexes, involved maintenance response to Sororin-depleted cells reach prometaphase with are able form metaphase plates. However,...
In bacterial plasmids, Rep proteins initiate DNA replication by undergoing a structural transformation coupled to dimer dissociation. Amyloidogenesis of the ‘winged-helix’ N-terminal domain RepA (WH1) is triggered in vitro upon binding plasmid-specific sequences, and occurs at nucleoid vivo. Amyloid fibers are made distorted RepA-WH1 monomers that assemble as single or double intertwined tubular protofilaments. causes E. coli an amyloid proteinopathy, which transmissible from mother daughter...