A5052770600- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Glycosylation and Glycoproteins Research
- Histone Deacetylase Inhibitors Research
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Chromosomal and Genetic Variations
- Cellular transport and secretion
- Chemical Synthesis and Analysis
- Protein Degradation and Inhibitors
- Biochemical and Molecular Research
- Micro and Nano Robotics
- FOXO transcription factor regulation
- Chemical Synthesis and Characterization
- Sirtuins and Resveratrol in Medicine
- Advanced Electron Microscopy Techniques and Applications
- Cytomegalovirus and herpesvirus research
- Genetics and Neurodevelopmental Disorders
- Plant nutrient uptake and metabolism
- DNA and Nucleic Acid Chemistry
- Photosynthetic Processes and Mechanisms
- Pharmacology and Obesity Treatment
Institute of Cancer Research
2021-2024
MRC Laboratory of Molecular Biology
2016-2021
Google (United States)
2017
European Molecular Biology Laboratory
2011-2013
European Institute of Oncology
2012
European Molecular Biology Laboratory
2011
Abstract Accurate mitosis is coordinated by the spindle assembly checkpoint (SAC) through mitotic complex (MCC), which inhibits anaphase-promoting or cyclosome (APC/C). As an essential regulator, Cdc20 promotes exit activating APC/C and monitors kinetochore-microtubule attachment SAC. requires multiple interactions with MCC subunits to elicit these functions. Functionally assessing within cells efficient depletion of endogenous Cdc20, highly difficult achieve RNA interference (RNAi). Here we...
Drosophila Nurf55 is a component of different chromatin-modifying complexes, including the PRC2 (Polycomb repressive complex 2). Based on 1.75-Å crystal structure bound to histone H4 helix 1, we analyzed interactions (Nurf55 or p55 in fly and RbAp48/46 human) with N-terminal tail H3, first H4, an fragment subunit Su(z)12 using isothermal calorimetry pulldown experiments. Site-directed mutagenesis identified binding site H3 at top WD40 propeller. Unmodified K9me3- K27me3-containing peptides...
Polycomb group (PcG) protein complexes repress developmental regulator genes by modifying their chromatin. How different PcG proteins assemble into and are recruited to target is poorly understood. Here, we report the crystal structure of core Drosophila complex Pleiohomeotic (Pho)-repressive (PhoRC), which contains response element (PRE)-binding Pho Sfmbt. The spacer region Pho, separated from DNA-binding domain a long flexible linker, forms tight with four malignant brain tumor (4MBT)...
Abstract Lysine acetylation in histone tails is a key post-translational modification that controls transcription activation. Histone deacetylase complexes remove acetylation, thereby repressing and regulating the transcriptional output of each gene. Although these are drug targets crucial regulators organismal physiology, their structure mechanisms action largely unclear. Here, we present complete human SIN3B holo-complex with without substrate mimic. Remarkably, encircles contacts its...
Article19 April 2020Open Access Source Data A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase Claudio Alfieri Corresponding Author [email protected] orcid.org/0000-0003-3215-1607 MRC Laboratory Molecular Biology, Cambridge, UK Search for more papers by this author Thomas Tischer orcid.org/0000-0002-6845-2762 David Barford orcid.org/0000-0001-8810-950X Information *,1,†, Tischer1 and Barford1 1MRC †Present address: Institute Cancer Research, London,...
The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that controls cell cycle transitions. Its regulation by the spindle assembly checkpoint (SAC) coordinated with attachment of sister chromatids to mitotic spindle. APC/C SUMOylation on APC4 ensures timely anaphase onset and chromosome segregation. To understand structural functional consequences SUMOylation, we reconstituted SUMOylated for electron cryo-microscopy biochemical analyses. causes a substantial...
Abstract Genes encoding the core cell cycle machinery are transcriptionally regulated by MuvB family of protein complexes in a cycle-specific manner. Complexes with transcription factors B-MYB and FOXM1 activate mitotic genes during proliferation. The mechanisms transcriptional regulation these still poorly characterised. Here, we combine biochemical analysis vitro reconstitution, structural cryo-electron microscopy cross-linking mass spectrometry, to functionally examine complexes. We find...
The proper control of mitosis depends on the ubiquitin-mediated degradation right mitotic regulator at time. This is effected by Anaphase Promoting Complex/Cyclosome (APC/C) ubiquitin ligase that regulated Spindle Assembly Checkpoint (SAC). SAC prevents APC/C from recognising Cyclin B1, essential anaphase and cytokinesis inhibitor, until all chromosomes are attached to spindle. Once attached, B1 rapidly degraded enable chromosome segregation cytokinesis. We have a good understanding how...
Abstract Accurate chromosome segregation is coordinated by the spindle assembly checkpoint (SAC) through its effector mitotic complex (MCC), to inhibit anaphase-promoting or cyclosome (APC/C). Cdc20 an essential regulator since it promotes exit activating APC/C and monitors kinetochore-microtubule attachment SAC. The proper functioning of requires multiple interactions with MCC subunits. To functionally assess each these within cells efficient depletion endogenous Cdc20, which highly...
Abstract Histone deacetylase complexes remove histone lysine acetylation, a key post-translational modification that activates transcription at each gene. Although these are drug targets and crucial regulators of organismal physiology, their structure mechanisms action largely unclear. Here, we present the first complete human SIN3B holo-complex with without substrate mimic. Remarkably, encircles contacts its allosteric basic patch thereby stimulating catalysis. A loop inserts into catalytic...
ABSTRACT The proper control of mitosis depends on the ubiquitin-mediated degradation right mitotic regulator at time. This is under anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase that regulated by Spindle Assembly Checkpoint (SAC). prevents APC/C from recognizing Cyclin B1, essential and cytokinesis inhibitor, until all chromosomes are attached to spindle. Once attached, B1 rapidly degraded enable chromosome segregation cytokinesis. We have a good understanding how SAC...