A5045705655- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Cellular Mechanics and Interactions
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- Protist diversity and phylogeny
- Nuclear Structure and Function
- Advanced Fluorescence Microscopy Techniques
- Ubiquitin and proteasome pathways
- Reproductive Biology and Fertility
- Plant Molecular Biology Research
- Ion channel regulation and function
- DNA Repair Mechanisms
- Prenatal Screening and Diagnostics
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Mitochondrial Function and Pathology
- Cell Image Analysis Techniques
- CRISPR and Genetic Engineering
- Fungal and yeast genetics research
- Gene expression and cancer classification
- Oceanographic and Atmospheric Processes
- Advanced Materials and Mechanics
- Enzyme Structure and Function
University of Warwick
2015-2024
University Hospital Coventry
2021
Yale University
2018
Google (United States)
2012
Marie Curie
2006-2010
Marine Biological Laboratory
2010
Massachusetts Institute of Technology
2003-2006
IIT@MIT
2006
The Gurdon Institute
1999-2004
University of Cambridge
1999-2004
Human beings are made of ~50 trillion cells which arise from serial mitotic divisions a single cell - the fertilised egg. Remarkably, early human embryo is often chromosomally abnormal, and many mosaic, with karyotype differing one to another. Mosaicism presumably arises chromosome segregation errors during divisions, although these events have never been visualised in living embryos. Here, we establish live imaging using normally embryos an egg-share-to-research programme, as well...
Kinetochores are multiprotein complexes that assemble on centromeric DNA and attach chromosomes to spindle microtubules. Over the past six years, number of proteins known localize Saccharomyces cerevisiae kinetochore has increased from around 10 over 60. However, relatively little is about protein-protein interactions mediate assembly or overall structure microtubule-attachment sites. Here we used biophysical techniques, affinity purification, mass spectrometry, in vivo assays examine state...
Abstract Background Kinetochores are large multi-protein structures that assemble on centromeric DNA ( CEN DNA) and mediate the binding of chromosomes to microtubules. Comprising 125 base-pairs 70 or more protein components, Saccharomyces cerevisiae kinetochores among best understood. In contrast, most fungal, plant animal cells s longer complex, raising question whether kinetochore architecture has been conserved through evolution, despite considerable divergence in sequence. Results Using...
During mitosis in most eukaryotic cells, chromosomes align and form a metaphase plate halfway between the spindle poles, about which they exhibit oscillatory movement. These movements are accompanied by changes distance sister kinetochores, commonly referred to as breathing. We developed live cell imaging assay combined with computational image analysis quantify properties dynamics of kinetochores three dimensions. show that baseline oscillation breathing speeds late prometaphase set...
In animal somatic cells, bipolar spindle formation requires separation of the centrosome-based poles. Centrosome relies on multiple pathways, including cortical forces and antiparallel microtubule (MT) sliding, which are two activities controlled by protein kinase aurora A. We previously found that depletion human kinetochore Mcm21RCENP-O results in monopolar spindles, raising question as to whether kinetochores contribute centrosome separation. this study, we demonstrate promote after...
There are two main pathways in eukaryotic cells for the repair of DNA double-strand breaks: homologous recombination and nonhomologous end joining. Because genomes packaged chromatin, these likely to require modulation chromatin structure. One way achieve this is by acetylation lysine residues on N-terminal tails histones. Here we demonstrate that Sin3p Rpd3p, components one predominant histone deacetylase complexes Saccharomyces cerevisiae , required efficient We also show 16 H4 becomes...
BackgroundKinetochores are large multiprotein complexes indispensable for proper chromosome segregation. Although Drosophila is a classical model organism studies of segregation, little known about the organization its kinetochores.Methodology/Principal FindingsWe employed bioinformatics, proteomics and cell biology methods to identify analyze interaction network kinetochore proteins. We have shown that three proteins highly diverged from human yeast Ndc80, Nuf2 Mis12 indeed their...
Microtubule-associated proteins of the mitotic spindle are thought to be important for initial assembly and maintenance structure function. However, distinguishing roles a given protein is difficult. Most experimental methods inactivation slow therefore affect both maintenance. Here, we have used 'knocksideways' rapidly (∼5 minutes) specifically remove TACC3-ch-TOG-clathrin non-motor complexes from kinetochore fibers (K-fibers). This method allows complex inactivated at defined stages...
Summary Roughly half of all animal somatic cell spindles assemble by the classical prophase pathway, in which centrosomes separate ahead nuclear envelope breakdown (NEBD). The remainder prometaphase following NEBD. Why cells use dual pathway spindle assembly is unclear. Here, examining timing NEBD relative to onset Eg5-mEGFP loading centrosomes, we show that a time window 9.2 ± 2.9 min available for Eg5-driven centrosome separation NEBD, and those succeed separating their within this...
The approximately thirty core subunits of kinetochores assemble on centromeric chromatin containing the histone H3 variant CENP-A and connect chromosomes with spindle microtubules. proximal 16-subunit CCAN (constitutive centromere associated network) creates a mechanically stable bridge between kinetochore's microtubule-binding machinery, 10-subunit KMN assembly. Here, we reconstituted stoichiometric 11-subunit human that forms when CENP-OPQUR complex binds to joint interface CENP-HIKM...
Centrosome amplification is a common feature of human tumors. To survive, cancer cells cluster extra centrosomes during mitosis, avoiding the detrimental effects multipolar divisions. However, it unclear whether clustering requires adaptation or inherent to all cells. Here, we show that have varied abilities centrosomes. Epithelial are innately inefficient at even in presence HSET/KIFC1, which essential but not sufficient promote clustering. The E-cadherin decreases cortical contractility...
Significance During cell division, molecular motors from the kinesin superfamily, in particular Kinesin-12 (Kif15) and Kinesin-5 (Eg5), play a crucial role formation of spindle—a bipolar microtubule array that is essential for accurate chromosome segregation. While Eg5 well studied, mechanism by which Kif15 maintains spindle bipolarity absence unknown. In this work we reconstitute on dynamic microtubules vitro. We reveal multi-function motor cross-links drives transport one along other,...
Aneuploid human eggs (oocytes) are a major cause of infertility, miscarriage, and chromosomal disorders. Such aneuploidies increase greatly as women age, with defective linkages between sister chromatids (cohesion) in meiosis common cause. We found that loss specific pool the cohesin protector protein, shugoshin 2 (SGO2), may contribute to this phenomenon. Our data indicate SGO2 preserves chromatid cohesion by protecting "cohesin bridge" chromatids. In oocytes, localizes both sub-centromere...