A5055723260- DNA Repair Mechanisms
- Neuropeptides and Animal Physiology
- Microtubule and mitosis dynamics
- Receptor Mechanisms and Signaling
- Photosynthetic Processes and Mechanisms
- Biocrusts and Microbial Ecology
- Neuroscience and Neuropharmacology Research
- Genomics and Chromatin Dynamics
- Photoreceptor and optogenetics research
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Endodontics and Root Canal Treatments
- Light effects on plants
- Neutropenia and Cancer Infections
- Enzyme Structure and Function
- Bone Tissue Engineering Materials
- Plant Stress Responses and Tolerance
- RNA Interference and Gene Delivery
- Polyomavirus and related diseases
- Protein Kinase Regulation and GTPase Signaling
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
- Cancer therapeutics and mechanisms
- Chemical Synthesis and Analysis
- Mitochondrial Function and Pathology
University of Oxford
2016-2024
John Radcliffe Hospital
2023-2024
MRC Weatherall Institute of Molecular Medicine
2023-2024
CRUK/MRC Oxford Institute for Radiation Oncology
2019-2021
Medical Research Council
2016-2020
Cancer Research UK
2016-2020
Google (United States)
2017
University of Leicester
2006-2007
Universidad Autónoma de Madrid
2000-2004
The cytotoxicity of DNA-protein crosslinks (DPCs) is largely ascribed to their ability block the progression DNA replication. DPCs frequently occur in cells, either as a consequence metabolism or exogenous agents, but mechanism DPC repair not completely understood. Here, we characterize SPRTN specialized DNA-dependent and replication-coupled metalloprotease for repair. cleaves various binding substrates during S-phase thus protects proliferative cells from toxicity. Ruijs-Aalfs syndrome...
Abstract Eukaryotic topoisomerase 1 (TOP1) regulates DNA topology to ensure efficient replication and transcription. TOP1 is also a major driver of endogenous genome instability, particularly when its catalytic intermediate—a covalent TOP1-DNA adduct known as cleavage complex (TOP1cc)—is stabilised. TOP1ccs are highly cytotoxic failure resolve them underlies the pathology neurological disorders but exploited in cancer therapy where target widely used frontline anti-cancer drugs. A critical...
Article15 October 2019Open Access Source DataTransparent process The p97–Ataxin 3 complex regulates homeostasis of the DNA damage response E3 ubiquitin ligase RNF8 Abhay Narayan Singh Department Oncology, Cancer Research UK/Medical Council Oxford Institute for Radiation University Oxford, UK Search more papers by this author Judith Oehler Ignacio Torrecilla Susan Kilgas Shudong Li Bruno Vaz Claire Guérillon Novo Nordisk Foundation Center Protein Research, Copenhagen, Denmark John Fielden...
We demonstrate a role for protein kinase casein 2 (CK2) in the phosphorylation and regulation of M3-muscarinic receptor transfected cells cerebellar granule neurons. On agonist occupation, specific subsets phosphoacceptor sites (which include SASSDEED motif third intracellular loop) are phosphorylated by CK2. Receptor mediated CK2 specifically regulates coupling to Jun-kinase pathway. Importantly, other phosphorylation-dependent processes regulated kinases distinct from conclude that G...
Abstract We investigated the possibility of Ca2+ signaling in cyanobacteria (blue-green algae) by measuring intracellular free levels ([Ca2+]i) a recombinant strain nitrogen fixing cyanobacteriumAnabaena sp. PCC7120, which constitutively expresses Ca2+-binding photoprotein apoaequorin. The homeostasis response to increasing external has been studied this strain. resting level Anabaena was found be between 100 and 200 nm. Additions concentrations gave transient burst [Ca2+]i followed very...
Abstract The SPRTN metalloprotease is essential for DNA-protein crosslink (DPC) repair and DNA replication in vertebrate cells. Cells deficient protease exhibit DPC-induced stress genome instability, manifesting as premature ageing liver cancer. Here, we provide a body of evidence suggesting that activates the ATR-CHK1 phosphorylation signalling cascade during physiological by proteolysis-dependent eviction CHK1 from replicative chromatin. During this process, proteolyses...
The impact of calcium signals in virtually all cells has led to the study their role prokaryotic organisms as stress response modulators. Cell differentiation adverse conditions is a common Ca 2+ -requiring response. Nitrogen starvation induces N 2 -fixing heterocysts filamentous cyanobacterium Anabaena sp. PCC7120. This paper reports use recombinant strain this organism expressing photoprotein aequorin monitor intracellular free-calcium concentration during course heterocyst...
The human ether-a-go-go related gene (hERG) potassium channel is expressed in a variety of tissues including the heart, neurons and some cancer cells. hERG channels are modulated by several intracellular signalling pathways these provide important mechanisms for regulating cellular excitability. In this study, we investigated muscarinic modulation currents direct phosphorylation subunits HEK-293 cells at physiologically relevant temperatures protein kinase C (PKC). Activation G(alpha...
Abstract We show here that both salinity and osmotic stress trigger transient increases in intracellular free Ca 2+ concentration ([Ca ] i ) cells of the nitrogen‐fixing filamentous cyanobacterium Anabaena sp. PCC7120, which constitutively expresses apoaequorin. Isoosmolar concentrations salt (NaCl) osmoticum (sucrose) induced calcium transients similar magnitude shape, suggesting sense, via signalling, mostly stress. The by NaCl sucrose were completely blocked chelator ethylene...
Abstract DNA–protein crosslinks (DPCs) are toxic DNA lesions wherein a protein is covalently attached to DNA. If not rapidly repaired, DPCs create obstacles that disturb replication, transcription and damage repair, ultimately leading genome instability. The persistence of associated with premature ageing, cancer neurodegeneration. In mammalian cells, the repair mainly relies on proteolytic activities SPRTN 26S proteasome, complemented by other enzymes including TDP1/2 MRN complex, many...
Abstract The human MRE11/RAD50/NBS1 (MRN) complex plays a crucial role in sensing and repairing DNA DSB. MRE11 possesses dual 3′−5′ exonuclease endonuclease activity forms the core of multifunctional MRN complex. We previously identified C-terminally truncated form (TR-MRE11) associated with post-translational degradation. Here we SPRTN as essential protease for formation TR-MRE11 characterised this its damage response (DDR). Using tandem mass spectrometry site-directed mutagenesis,...
Changes in synaptic strength mediated by ionotropic glutamate N-methyl-d-asparate (NMDA) receptors is generally considered to be the molecular mechanism underlying memory and learning. NMDA themselves are subject regulation through signaling pathways that activated G-protein-coupled (GPCRs). In this study we investigate ability of regulate GPCRs focusing on Gq/11-coupled M3-muscarinic receptor expressed endogenously mouse cerebellar granule neurons. We show activation results phosphorylation...
ABSTRACT Light‐to‐dark transitions represent one of the most crucial environmental stresses that photosynthetic organisms must cope with, since substantial metabolism adaptations are required in order to utilize alternative energy and carbon sources. Although signal transduction systems for changing light regimes not sufficiently understood, calcium has been implicated plants as a second messenger light‐on light‐off events. Much less is known about signalling cyanobacteria, but it shown...
Abstract The SPRTN metalloprotease is essential for DNA-protein crosslink (DPC) repair and DNA replication in vertebrate cells. Cells deficient protease activity exhibit severe DPC-induced stress genome instability, manifesting as premature ageing liver cancer humans mice. Strikingly, SPRTN-deficient cells also show a G2/M checkpoint defect fail to activate robust kinase 1 (CHK1) signalling cascade normally triggered response stress. Here, we that activates the CHK1 during physiological...