A5101466701- DNA Repair Mechanisms
- Receptor Mechanisms and Signaling
- CRISPR and Genetic Engineering
- Bacterial Genetics and Biotechnology
- Signaling Pathways in Disease
- Protein Structure and Dynamics
- Advanced Electron Microscopy Techniques and Applications
- RNA and protein synthesis mechanisms
- Graphene research and applications
- RNA Research and Splicing
- Carbon Nanotubes in Composites
- Mitochondrial Function and Pathology
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- Histone Deacetylase Inhibitors Research
- Cancer-related gene regulation
- Fullerene Chemistry and Applications
The Francis Crick Institute
2016-2021
Imperial College London
2013-2015
Histone lysine methyltransferases (HKMTs) are an important class of targets for epigenetic therapy. 1 (chaetocin), epidithiodiketopiperazine (ETP) natural product, has been reported to be a specific inhibitor the SU(VAR)3-9 HKMTs. We have studied inhibition HKMT G9a by and functionally related analogues. Our results reveal that only structurally unique ETP core is required inhibition, such time-dependent irreversible (in absence DTT), ultimately resulting in protein denaturation. Mass...
Activation of the main DNA interstrand crosslink repair pathway in higher eukaryotes requires mono-ubiquitination FANCI and FANCD2 by FANCL, E3 ligase subunit Fanconi anemia core complex. form a stable complex; however, molecular basis their ubiquitination is ill defined. FANCL stimulated presence FANCB FAAP100 complex components, through an unknown mechanism. How achieved remains unclear. Here, we use structural electron microscopy, combined with crosslink-coupled mass spectrometry, to find...
Abstract The functions of cohesin are central to genome integrity, chromosome organization and transcription regulation through its prevention premature sister-chromatid separation the formation DNA loops. loading onto chromatin depends on Scc2–Scc4 complex; however, little is known about how it stimulates cohesion-loading activity. Here we determine large ‘hook’ structure Scc2 responsible for catalysing loading. We identify key surfaces that crucial in vivo . With aid previously determined...
We investigate the environmental stability of fullerene solutions by static and dynamic light scattering, FTIR, NMR mass spectroscopies, quantum chemical calculations. find that visible exposure in toluene, a good solvent, under ambient laboratory conditions results C60 oxidation to form epoxides, subsequently causes clustering solution. The clusters grow with time, even absence further illumination, can reach dimensions from ≈100 nm μm scale over ≈1 day. Static scattering suggests resulting...
Abstract The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision (NER) and inter-strand crosslink (ICLR). How is catalytically activated by junction substrates not currently understood. Here we report cryo-electron microscopy structures of both DNA-free DNA-bound human XPF-ERCC1. adopts an auto-inhibited conformation which the XPF helical domain masks ERCC1 (HhH) 2 restricts access to catalytic site. engagement releases...
RET receptor tyrosine kinase plays vital developmental and neuroprotective roles in metazoans. GDNF family ligands (GFLs) when bound to cognate GFRα co-receptors recognize activate stimulating its cytoplasmic function. The principles for ligand-co-receptor recognition are incompletely understood. Here, we report a crystal structure of the cadherin-like module (CLD1-4) from zebrafish revealing interdomain flexibility between CLD2 CLD3. Comparison with cryo-electron microscopy ligand-engaged...
Abstract The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision (NER) and inter-strand crosslink (ICLR). How is catalytically activated by junction substrates not currently understood. We report cryo-electron microscopy structures of both DNA-free DNA-bound human XPF-ERCC1. adopts an auto-inhibited conformation which the XPF helical domain masks ERCC1 DNA-binding elements restricts access to catalytic site. Binding a...
Abstract RET receptor tyrosine kinase plays vital developmental and neuroprotective roles in metazoans. G DNF family ligands (GFLs) when bound to cognate GFRα co-receptors recognise activate stimulating its cytoplasmic function. The principles for ligand-co-receptor recognition are incompletely understood. Here we report a crystal structure of the cadherin-like module (CLD1-4) from zebrafish revealing interdomain flexibility between CLD2-CLD3. Comparison with cryo-EM ligand-engaged ECD...