A5031379026- DNA Repair Mechanisms
- Cancer therapeutics and mechanisms
- Polyomavirus and related diseases
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Neutropenia and Cancer Infections
- Advanced biosensing and bioanalysis techniques
- Genetic Neurodegenerative Diseases
- Amyotrophic Lateral Sclerosis Research
- Lung Cancer Research Studies
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- Neurogenetic and Muscular Disorders Research
- Epigenetics and DNA Methylation
- Nutrition and Health in Aging
- Cancer-related molecular mechanisms research
- Antibiotics Pharmacokinetics and Efficacy
- Bioactive Compounds and Antitumor Agents
- Carcinogens and Genotoxicity Assessment
- Ubiquitin and proteasome pathways
- Muscle metabolism and nutrition
- Circular RNAs in diseases
University of Sheffield
2015-2024
University of Bradford
2021-2024
Zewail City of Science and Technology
2014-2023
Juntendo University Hospital
2022
University of Sussex
2006-2016
Wellcome Trust
2014-2016
Ain Shams University
2006-2013
The molecular role of poly (ADP-ribose) polymerase-1 in DNA repair is unclear. Here, we show that the single-strand break protein XRCC1 rapidly assembled into discrete nuclear foci after oxidative damage at sites synthesis. Poly synthesis peaks during a 10 min treatment with H2O2 and appearance shortly afterwards. Both decrease to background levels subsequent incubation drug-free medium, consistent rapidity process. formation was greatly reduced by mutation BRCT I domain physically interacts...
Topoisomerase II (Top2) activity involves an intermediate in which the topoisomerase is covalently bound to a DNA double-strand break via 5′-phosphotyrosyl bond. Although these intermediates are normally transient, they can be stabilized by antitumor agents that act as Top2 "poisons," resulting induction of cytotoxic breaks, and implicated formation site-specific translocations commonly associated with cancer. Recently, we revealed TRAF TNF receptor-associated protein (TTRAP) 5′-tyrosyl...
Aprataxin and polynucleotide kinase (PNK) are DNA end processing factors that recruited into the single- double-strand break repair machinery through phosphorylation-specific interactions with XRCC1 XRCC4, respectively. These mediated a divergent class of forkhead-associated (FHA) domain binds to peptide sequences in XRCC4 phosphorylated by casein 2 (CK2). Here, we identify product uncharacterized open reading frame C2orf13 as novel member this FHA family proteins denote protein APLF...
Abstract Hexanucleotide repeat expansions in the C9ORF72 gene are commonest known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Expression transcripts dipeptide proteins trigger multiple mechanisms neurotoxicity. How get exported from nucleus is unknown. Here, we show that depletion nuclear export adaptor SRSF1 prevents neurodegeneration locomotor deficits a Drosophila model C9ORF72-related disease. This intervention suppresses cell death patient-derived motor...
Carbon monoxide (CO)-releasing molecules (CORMs), mostly metal carbonyl compounds, are extensively used as experimental tools to deliver CO, a biological 'gasotransmitter', in mammalian systems. CORMs also explored potential novel antimicrobial drugs, effectively and rapidly killing bacteria vitro animal models, but reportedly benign towards cells. Ru-carbonyl CORMs, exemplified by CORM-3 (Ru(CO)3Cl(glycinate)), exhibit the most potent effects against Escherichia coli. We demonstrate that...
The affordable and reliable detection of Hepatitis C Virus (HCV) RNA is a cornerstone in the management control infection, affecting approximately 3% global population. However, existing technologies are expensive, labor intensive time consuming, posing significant limitations to their wide-scale exploitation, particularly economically deprived populations. Here, we utilized unique optical physicochemical properties gold nanoparticles (AuNPs) develop novel assay platform shown be rapid...
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...
The abortive activity of topoisomerases can result in clastogenic and/or lethal DNA damage which the topoisomerase is covalently linked to 3′- or 5′-terminus a strand break. This type implicated chromosome translocations and neurological disease underlies clinical efficacy an important class anticancer 'poisons'. Tyrosyl phosphodiesterase-1 protects cells from I (Top1) by hydrolyzing 3′-phosphotyrosyl bond that links Top1 break currently only known human enzyme displays this cells. Recently,...
Breaking and sealing one strand of DNA is an inherent feature chromosome metabolism to overcome torsional barriers. Failure reseal broken strands results in protein-linked breaks, causing neurodegeneration humans. This typified by defects tyrosyl phosphodiesterase 1 (TDP1), which removes stalled topoisomerase peptides from termini. Here we show that TDP1 a substrate for modification the small ubiquitin-like modifier SUMO. We purify SUMOylated mammalian cells identify SUMOylation site as...
Colorectal cancer is the third most common in world. Despite surgery, up to 50% of patients relapse with incurable disease. First-line chemotherapy uses topoisomerase 1 (TOP1) poison irinotecan, which triggers cell death by trapping TOP1 on DNA. The removal peptide from TOP1-DNA breaks conducted tyrosyl-DNA phosphodiesterase (TDP1). putative roles for TDP1 and colorectal cancer, their role cellular clinical responses TOP1-targeting therapies remains unclear. Here, we show varying expression...
Abstract Salmonella Typhi activates the host DNA damage response through typhoid toxin, facilitating symptoms and chronic infections. Here we reveal a non-canonical response, which call RING (response induced by genotoxin), characterized accumulation of phosphorylated histone H2AX (γH2AX) at nuclear periphery. is result persistent mediated toxin nuclease activity hyperphosphorylation RPA, sensor single-stranded (ssDNA) replication stress. The overloads RPA pathway with ssDNA substrate,...
Ataxia oculomotor apraxia-1 (AOA1) is an autosomal recessive neurodegenerative disease that results from mutations of aprataxin (APTX). APTX associates with the DNA single- and double-strand break repair machinery able to remove AMP 5'-termini at strand breaks in vitro. However, attempts establish a defect APTX-defective cells have proved conflicting unclear. We reasoned this may reflect 5'-AMP represent only minor subset induced cells, and/or availability alternative mechanisms for removing...