A5066229850- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- CRISPR and Genetic Engineering
- Cancer, Hypoxia, and Metabolism
- Autophagy in Disease and Therapy
- NF-κB Signaling Pathways
- Genetics, Aging, and Longevity in Model Organisms
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Healthcare Policy and Management
- Chronic Lymphocytic Leukemia Research
- Innovation and Socioeconomic Development
- Cancer and Skin Lesions
- Immune Response and Inflammation
- Skin Diseases and Diabetes
- Yersinia bacterium, plague, ectoparasites research
- Lymphoma Diagnosis and Treatment
- interferon and immune responses
- Bacillus and Francisella bacterial research
- Dermatologic Treatments and Research
- Endoplasmic Reticulum Stress and Disease
- Vector-borne infectious diseases
- RNA Research and Splicing
- ICT Impact and Policies
Newcastle University
2011-2025
Massachusetts General Hospital
2025
Newcastle Hospitals - Campus for Ageing and Vitality
2011
HIF1α (hypoxia inducible factor 1α) is the central regulator of cellular response to low oxygen and its activity deregulated in multiple human pathologies. Consequently, given importance HIF signaling disease, there considerable interest developing strategies modulate down-stream events. In present study we find that under hypoxic conditions, activation PERK branch unfolded protein (UPR) can suppress levels by preventing efficient translation. Activation inhibits de novo synthesis...
Abstract CYLD cutaneous syndrome (CCS) skin tumors develop from puberty onwards, can number in the hundreds and progressively grow over time. CCS patients lack medical therapies require repeated surgery to control tumor burden. loss of heterozygosity (LOH) drives growth, have previously been shown demonstrate increased canonical NF-κB Wnt signalling. Here, we evidence non-canonical signalling keratinocytes, with p100 p52 processing RelB protein expression compared normal skin. Utilizing...
The cellular response to hypoxia is characterised by a switch in the transcriptional program, mediated predominantly inducible factor family of transcription factors (HIF). Regulation HIF1 primarily controlled post-translational modification HIF1α subunit, which can alter its stability and/or activity. This study identifies an unanticipated role for X-linked inhibitor apoptosis (XIAP) protein as regulator Lys63-linked polyubiquitination HIF1α. ubiquitination XIAP dependent on activity E2...
Telomere attrition is linked to cancer, diabetes, cardiovascular disease and aging. This because telomere losses trigger further genomic modifications, culminating with loss of cell function malignant transformation. However, factors regulating the transition from cells short telomeres, profoundly altered genomes, are little understood. Here, we use budding yeast engineered lack telomerase other forms maintenance, screen for such factors. We show that initially, different DNA damage...
Abstract The nuclear factor-κB (NF-κB) family of transcription factors can directly or indirectly regulate many important areas biology, including immunity, inflammation and cell survival. One intriguing aspect NF-κB crosstalk with other signalling pathways is its regulation mitochondrial biogenesis, metabolism apoptosis. In addition to regulating the expression genes encoded in nucleus, components are also found within mitochondria themselves associated DNA. However, complete biochemical...
Replicative senescence is a permanent cell cycle arrest in response to extensive telomere shortening. To understand the mechanisms behind arrest, we screened for factors affecting replicative budding yeast lacking elongation pathways. Intriguingly, found that DNA polymerase epsilon (Pol ε) acts synergistically with Exo1 nuclease maintain senescence. In contrast, Pol ε-associated checkpoint and replication protein Mrc1 facilitates escape from this paradox, which DNA-synthesizing cooperate...
Thermal regulation of gene expression occurs in many microorganisms, and is mediated via several typical mechanisms. Yersinia pestis the causative agent plague spreads by zoonotic transfer from fleas to mammalian blood with a concomitant rapid temperature change, ambient 37 °C, which induces capsular antigen (Caf1) that inhibits phagocytosis. Caf1 formed into long polymeric fimbriae periplasmic chaperone (Caf1M) outer membrane usher (Caf1A). All three are encoded on an operon regulated...
The development of resistance and the activation bypass pathway signalling represents a major problem for clinical application protein kinase inhibitors. While investigating effect either c-Rel deletion or RelAT505A phosphosite knockin on Eµ-Myc mouse model B-cell lymphoma, we discovered that both NF-κB subunit mutations resulted in CHK1 inhibitor resistance, arising from loss alteration activity, respectively. However, since lymphomas depend activity to cope with high levels DNA replication...
Damaged DNA can be repaired by removal and re-synthesis of up to 30 nucleotides during base or nucleotide excision repair. An important question is what happens when many more are removed, resulting in long single-stranded (ssDNA) lesions. Such lesions appear on chromosomes telomere damage, double strand break repair after the UV damage stationary phase cells. Here, we show that lesions, formed at dysfunctional telomeres budding yeast, re-synthesized cells removed from telomere-damaging...