A5030514934- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Photosynthetic Processes and Mechanisms
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Developmental Biology and Gene Regulation
- Plant nutrient uptake and metabolism
- Biochemical and Molecular Research
- Cancer Research and Treatments
- Plant Molecular Biology Research
- Nanoplatforms for cancer theranostics
- Cancer, Hypoxia, and Metabolism
- DNA and Nucleic Acid Chemistry
- RNA modifications and cancer
- Metabolism, Diabetes, and Cancer
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- Plant Virus Research Studies
- Fungal and yeast genetics research
- Gene expression and cancer classification
- Cancer therapeutics and mechanisms
Wellcome Centre for Cell Biology
2004-2023
University of Edinburgh
2008-2023
Wellcome Trust
2012
University of Dundee
1990-1995
Centro de Biología Molecular Severo Ochoa
1990-1992
Universidad Autónoma de Madrid
1991-1992
Consejo Superior de Investigaciones Científicas
1992
We have performed a biochemical and double-stranded RNA-mediated interference (RNAi) analysis of the role two chromosomal passenger proteins, inner centromere protein (INCENP) aurora B kinase, in cultured cells Drosophila melanogaster. INCENP function is tightly interlinked. The proteins bind to each other vitro, DmINCENP required for DmAurora localize properly mitosis as histone H3 kinase. accumulation at centromeres transfer spindle anaphase. RNAi either dramatically inhibited ability...
Survivin is an essential chromosomal passenger protein whose function remains unclear. Here, we have used RNA interference to specifically repress in cultured HeLa cells. Immunoblot analysis showed that was no longer detectable cultures 60 hours after transfection with Survivin-specific siRNA. Live cell many Survivin-depleted cells were delayed mitosis, and immunofluorescence of fixed specimens revealed accumulated prometaphase misaligned chromosomes. The proteins, INCENP Aurora-B, which can...
A number of lines evidence point to a predominance cytokinesis defects in spermatogenesis hypomorphic alleles the Drosophila polo gene. In pre-meiotic mitoses, result cysts primary spermatocytes with reduced numbers cells that can contain multiple centrosomes. These are connected by correspondingly ring canals, structures formed stabilization cleavage furrow. The earliest during meiotic divisions failure form correct mid-zone and mid-body at telophase. This is accompanied correctly localize...
The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the sister kinetochores each chromosome attached to microtubules from opposite spindle poles prior segregation anaphase. Initial attachments chromosomes involve random interactions between dynamic microtubules, errors occur frequently during early stages process. balance microtubule binding error correction (e.g., release bound microtubules) requires B with promoting...
Abstract The development of non-genotoxic therapies that activate wild-type p53 in tumors is great interest since the discovery as a tumor suppressor. Here we report identification over 100 small-molecules activating cells. We elucidate mechanism action chiral tetrahydroindazole (HZ00), and through target deconvolution, deduce its active enantiomer ( R )-HZ00, inhibits dihydroorotate dehydrogenase (DHODH). specificity HZ05, more potent analog, revealed by crystal structure )-HZ05/DHODH...
Multiple asters (MAST)/Orbit is a member of new family nonmotor microtubule-associated proteins that has been previously shown to be required for the organization mitotic spindle. Here we provide evidence MAST/Orbit functional kinetochore attachment, chromosome congression, and maintenance spindle bipolarity. In vivo analysis Drosophila mast mutant embryos undergoing early divisions revealed chromosomes are unable reach stable metaphase alignment bipolar spindles collapse as centrosomes move...
To identify sequences from the centromeric region, we have constructed a Drosophila melanogaster yeast artificial chromosome (YAC) library and screened it with purified DNA minichromosome Dp(1;f)1187 derived X chromosome. We describe structure of one clone isolated in this way. This YAC is structurally unstable contains tandemly repeated G+C-rich 11-mer 12-mer units, which call dodeca satellite. Most satellite located near centromere an autosome. Cross-hybridizing are found genomes organisms...
ABSTRACT ND10, otherwise known as nuclear dots, PML bodies or PODs, are punctate foci in interphase nuclei that contain several cellular proteins. The functions of ND10 have not been well defined, but they sensitive to external stimuli such stress and virus infection, disrupted malignant promyelocytic leukaemia cells. Herpes simplex type 1 regulatory protein Vmw110 induces the proteasome-dependent degradation component proteins Sp100, particularly species these which covalently conjugated...
Mutations at abnormal spindle result in abnormally long and wavy microtubules the meiotic spindles of males. Some these have a single pole take form unopposed hemi-spindles. Unfertilised eggs produced by homozygous asp females may either no nuclei, or small number large consistent with there also being an effect upon female meiosis. Such display free centrosomes independent arrays microtubules. Embryos that this phenotype are present among progeny fertilised females, together embryos undergo...
Aurora kinases are central regulators of mitotic-spindle assembly, chromosome segregation and cytokinesis. B is a member the chromosomal passenger complex (CPC) with crucial functions in regulation attachment kinetochores to microtubules We report here that contains conserved SUMO modification motif within its kinase domain. can bind peptides vitro when bound IN-box domain CPC partner INCENP. Mutation Lys207 arginine (Aurora BK207R) impairs formation conjugates vivo. Expression SUMO-null...
Spindle formation in female meiosis differs from mitosis many animals,as it takes place independently of centrosomes, and the molecular requirements this pathway remain to be understood. Here, we report two crucial roles Incenp, an essential subunit chromosomal passenger complex (the Aurora B complex), centrosome-independent spindle Drosophilafemale meiosis. First, initial assembly microtubules is drastically delayed incenp mutant. This clearly demonstrates,for first time, a role for Incenp...
DNA topoisomerase II (Topo II) is a major component of mitotic chromosomes and an important drug target in cancer chemotherapy, however, its role chromosome structure dynamics remains controversial. We have used RNAi to deplete Topo Drosophila S2 cells order carry out detailed functional analysis the protein during mitosis. find that not required for assembly kinetochore or targeting chromosomal passenger proteins, nonetheless, it essential anaphase sister chromatid separation. In response...
INCENP and aurora-B kinase are two chromosomal passenger proteins that thought to play key roles in coordinating chromosome segregation with cytokinesis somatic cells. Here we have analyzed their subcellular distribution, of phosphorylated histone H3, the timing relative appearance mouse spermatocytes during both meiotic divisions. Our results show mitotic spermatogonial cells, same pattern distribution as they do cultured labels synaptonemal complex central element from zygotene up late...
We have used fluorescence in situ hybridisation to wild-type and rearranged mitotic chromosomes map the Drosophila melanogaster dodecasatellite sequence. It is located at a unique site, within pericentric heterochromatin of right arm third chromosome, closely linked primary constriction. In polytene chromosomes, found as one or few dots central region chromocentre. untreated diploid cells, sequences are two throughout cell cycle. This distribution can be altered cycle-dependent manner ways....
The events of cell division are regulated by a complex interplay between kinases and phosphatases. Cyclin-dependent (Cdks), polo-like (Plks) Aurora play central roles in this process. Polo kinase (Plk1 humans) regulates wide range mitosis cytokinesis. To ensure the accuracy these processes, polo activity itself is subject to regulation. Phosphorylation its T loop (or activation loop) increases several-fold. It has been shown that A kinase, with co-factor Bora, activates Plk1 G(2), essential...