A5076929218- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Click Chemistry and Applications
- Advanced Biosensing Techniques and Applications
- Protein Degradation and Inhibitors
- Cytokine Signaling Pathways and Interactions
- Advanced Fluorescence Microscopy Techniques
The Francis Crick Institute
2023-2024
GlaxoSmithKline (United Kingdom)
2019-2021
Abstract RAD52 is important for the repair of DNA double-stranded breaks 1,2 , mitotic synthesis 3–5 and alternative telomere length maintenance 6,7 . Central to these functions, promotes annealing complementary single-stranded (ssDNA) 8,9 provides an BRCA2/RAD51-dependent homologous recombination 10 Inactivation in homologous-recombination-deficient BRCA1 - or BRCA2 -defective cells synthetically lethal 11,12 aberrant expression associated with poor cancer prognosis 13,14 As a consequence,...
Homologous recombination (HR) is essential for error-free repair of DNA double-strand breaks, perturbed replication forks (RFs), and post-replicative single-stranded (ssDNA) gaps. To initiate HR, the mediator tumor suppressor protein BRCA2 facilitates nucleation RAD51 on ssDNA prior to stimulation filament growth by paralogs. Although binding has been implicated in nucleation, function double-stranded (dsDNA) remains unclear. Here, we exploit single-molecule (SM) imaging visualize...
Malfunctions in the basic epigenetic mechanisms such as histone modifications, DNA methylation, and chromatin remodeling are implicated a number of cancers immunological neurodegenerative conditions. Within GlaxoSmithKline (GSK) we have utilized variations NanoBRET technology for direct measurement compound-target engagement within native cellular environments to drive high-throughput, routine structure-activity relationship (SAR) profiling across differing targets. is variation...
The predominant assay detection methodologies used for enzyme inhibitor identification during early-stage drug discovery are fluorescence-based. Each fluorophore has a characteristic fluorescence decay, known as the lifetime, that occurs throughout nanosecond-to-millisecond timescale. measurement of lifetime reporter biological activity is less common than intensity, even though latter numerous issues can lead to false-positive readouts. confirmation hit compounds true inhibitors requires...