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Amyotrophic lateral sclerosis (ALS) is a rapidly disabling and fatal neurodegenerative disease. Due to insufficient disease-modifying treatments, there is an unmet and urgent need for elucidating disease mechanisms that occur...

DNA damage response frontotemporal dementia Genome instability neurodegeneration Repeat Expansion Amyotrophic Lateral Sclerosis Amyotrophic Lateral Sclerosis DNA Damage Humans

The DNA damage response (DDR) fulfils essential roles to preserve genome integrity. Targeting the DDR in tumors has had remarkable success over the last decade, exemplified by the licensing of PARP inhibitors for cancer therapy....

DNA damage response DNA Repair PARP inhibitors PD-1 PD-L1 STING cGAS Immunotherapy Adaptive Immunity DNA Damage DNA Repair Discoidin Domain Receptors Humans Immune Checkpoint Inhibitors Immunity Cellular Immunotherapy Neoplasms Poly(ADP-ribose) Polymerase Inhibitors Protein Kinase Inhibitors

CRISPR-Cas9 genome engineering has revolutionised high-throughput functional genomic screens. However, recent work has raised concerns regarding the performance of CRISPR-Cas9 screens using TP53 wild-type human cells due to a...

Short Report Genetics and Genomics CRISPR screening TP53 DNA damage response human

ATM DNA damage response Cancer cancer therapy ionising radiation miR-34a miRNA p53 protein phosphatase protein phosphatase 1γ 3' Untranslated Regions Algorithms Blotting Western Cell Line Tumor DNA Damage Gene Expression Regulation Neoplastic Humans MicroRNAs Phosphorylation Protein Phosphatase 1 RADIATION Ionizing Tumor Suppressor Protein p53

Intracellular signals triggered by DNA breakage flow through proteins containing BRCT (BRCA1 C-terminal) domains. This family, comprising 23 conserved phosphopeptide-binding modules in man, is inaccessible to small-molecule...

BRCA1 BRCT domain DNA damage response drug-like inhibitor lead discovery Structure-Activity Relationship BRCA1 Protein Cell Survival Cells Cultured Fluorescence Resonance Energy Transfer HEK293 Cells Humans Molecular Dynamics Simulation Molecular Structure Phosphopeptides Protein Domains Signal Transduction Structure-Activity Relationship

The tumour suppressor p53, a stress-responsive transcription factor, plays a central role in cellular senescence. The role of p53 in senescence-associated stable proliferative arrest has been extensively studied. However...

DNA damage response SASP p53 Senescence Transcription Tumor Suppressor Protein p53 Marathon Running Phenotype Cellular Senescence

Cells exposed to hypoxia experience replication stress but do not accumulate DNA damage, suggesting sustained DNA replication. Ribonucleotide reductase (RNR) is the only enzyme capable of de novo synthesis of deoxyribonucleotide...

DNA damage response p53 RNR RRM2B Hypoxia Nucleotides radiosensitivity replication stress Animals Apoptosis Cell Cycle Proteins Colonic Neoplasms DNA Damage DNA Replication DNA Neoplasm Female HCT116 Cells Humans Mice Inbred BALB C Mice Nude Oxygen RNA Interference Radiation Tolerance Ribonucleoside Diphosphate Reductase Ribonucleotide Reductases Time Factors Transfection Tumor Burden Tumor Hypoxia Tumor Suppressor Proteins Xenograft Model Antitumor Assays

The human DNA damage response (DDR) triggers profound changes in gene expression, whose nature and regulation remain uncertain. Although certain micro-(mi)RNA species including miR34, miR-18, miR-16 and miR-143 have been...

AP-1 activator protein-1 DDR DNA damage response DNA damage response E2F1 transcription factor E2F1 FOXM1 forkhead box protein M1 NF-k B nuclear factor-k B NGS next-generation sequencing TF transcription factor TP53 tumour protein p53 clinical outcome computational analysis double stranded DNA breaks DSBs ionizing radiation IR miRNA micro-RNA micro-RNA misc RNA miscellaneous RNA next-generation sequencing p53 scRNA small cytoplasmic RNA snRNA small nuclear RNA snoRNA small nucleolar RNA tRNA transfer RNA Cell Line DNA Damage DNA Repair Gene Expression Regulation Gene Expression Regulation Neoplastic Genome Genome Human Humans MicroRNAs Neoplasms Organ Specificity Tumor Suppressor Protein p53

Rifl, the ortholog of the yeast Rapl interacting factor 1, a telomere length regulator was identified. Immunofluorescence did not reveal an association of human Rifl with telomeres. Preliminary co-immunoprecipitation with known...

Rif1 DNA damage response Rap1 human telomeres Life Sciences

BRCA1 BRCT DNA damage response Phosphopeptide Tandem BRCT domains pSXXF motif Amino Acid Motifs Amino Acid Sequence BRCA1 Protein Binding Sites Computer Simulation DNA Damage DNA Repair Models Chemical Models Molecular Molecular Sequence Data Phosphopeptides Protein Binding Protein Conformation Protein Structure Tertiary

Herpes simplex virus 1 (HSV-1) has extensive interactions with the host DNA damage response (DDR) machinery that can be either detrimental or beneficial to the virus. Proteins in the homologous recombination pathway are known to...

DDR DNA damage response HSV-1 PAXX c-NHEJ classical non-homologous end joining herpes simplex virus 1 Animals Cell Line DNA End-Joining Repair DNA-Binding Proteins Genes Viral Genome Viral Herpes Simplex Herpesvirus 1 Human Humans Interferons Mice Viral Proteins Virion Virus Replication

DNA damage response MLN4924 NEDD8 double-strand break repair Ubiquitin DNA DNA Damage DNA Repair DNA-Binding Proteins Humans Models Genetic NEDD8 Protein Protein Processing Post-Translational Ubiquitin-Protein Ligases Ubiquitination Ubiquitins

CHIP DNA damage response PPM1D cisplatin clonal hematopoiesis Doxorubicin Etoposide t-AML t-MDS topoisomerase inhibitors

article carcinogen 3D culture Benzo[a]pyrene human tissue organoid CYP1A1 NQO1 DNA Adducts RT-qPCR DNA damage response

AIMS: Oxidative damage and an associated DNA damage response (DDR) are evident in mild cognitive impairment and early Alzheimer's disease, suggesting that neuronal dysfunction resulting from oxidative DNA damage may account for...

Ageing brain Alzheimer's DNA damage response Dementia microarray neurones Aged 80 and over aging Alzheimer Disease Blotting Western Brain Cholesterol DNA Damage Female Humans Immunohistochemistry Laser Capture Microdissection Male Neurons Oligonucleotide Array Sequence Analysis Real-Time Polymerase Chain Reaction Signal Transduction Transcriptome

Organoids are 3D cultures that to some extent reproduce the structure, composition and function of the mammalian tissues from which they derive, thereby creating in vitro systems with more in vivo-like characteristics than 2D...

3D culture CYP1A1 DNA Adducts DNA damage response NQO1 RT-qPCR Benzo[a]pyrene carcinogen human tissue organoid Humans activation Metabolic Benzo(a)pyrene Cytochrome P-450 CYP1A1 DNA Adducts Liver Organoids