A5069098638- DNA Repair Mechanisms
- Carcinogens and Genotoxicity Assessment
- Cancer-related Molecular Pathways
- Language, Metaphor, and Cognition
- Syntax, Semantics, Linguistic Variation
- Genetic Neurodegenerative Diseases
- Inflammatory Bowel Disease
- Language, Discourse, Communication Strategies
- Natural Language Processing Techniques
- Linguistics and Discourse Analysis
- Mitochondrial Function and Pathology
- Gut microbiota and health
- Ubiquitin and proteasome pathways
- CRISPR and Genetic Engineering
- Lexicography and Language Studies
- Language, Linguistics, Cultural Analysis
- Microscopic Colitis
- RNA modifications and cancer
- RNA regulation and disease
- Microtubule and mitosis dynamics
- Telomeres, Telomerase, and Senescence
- RNA Research and Splicing
- PARP inhibition in cancer therapy
- Genomics and Chromatin Dynamics
- Eosinophilic Esophagitis
Tel Aviv University
2013-2025
Sheba Medical Center
2020-2025
Cancer Genetics (United States)
2024
Edmond and Lily Safra Children's Hospital
2023
Cincinnati Children's Hospital Medical Center
2015-2022
University of Cincinnati
2016-2022
Ben-Gurion University of the Negev
2005-2021
Hebrew University of Jerusalem
1981-2015
Heidelberg University
2008
German Cancer Research Center
2008
A gene, ATM , that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT characterized cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease genetically heterogeneous, with four complementation groups have been suspected to represent different genes. which has a transcript of 12 kilobases, found be patients...
The ATM protein, encoded by the gene responsible for human genetic disorder ataxia telangiectasia (A-T), regulates several cellular responses to DNA breaks. shares a phosphoinositide 3-kinase–related domain with proteins, some of them protein kinases. A wortmannin-sensitive kinase activity was associated endogenous or recombinant and abolished structural mutations. In vitro substrates included translation repressor PHAS-I p53 protein. phosphorylated in on single residue, serine-15, which is...
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency radiation sensitivity, and cancer predisposition. A-T heterozygotes are moderately prone. The gene, designated ATM, was recently identified in our laboratory by positional cloning, a partial cDNA clone found to encode polypeptide with PI-3 kinase domain. We report here the molecular cloning of contig spanning complete open reading frame ATM gene. predicted protein 3056 amino...
Quantitative phosphoproteomics suggests that kinases other than ATM participate in the initial phase of cellular response to DNA double-strand breaks.
Ataxia–telangiectasia (A-T) is a pleiotropic genome instability syndrome resulting from the loss of homeostatic protein kinase ATM. The complex phenotype A-T includes progressive cerebellar degeneration, immunodeficiency, gonadal atrophy, interstitial lung disease, cancer predisposition, endocrine abnormalities, chromosomal instability, radiosensitivity, and segmental premature aging. Cultured skin fibroblasts patients exhibit senescence, highlighting association between cellular We found...
The ataxia telangiectasiamutated (ATM) gene encodes a serine/threonine protein kinase that plays critical role in genomic surveillance and development. Here, we use peptide library approach to define the <i>in vitro</i> substrate specificity of ATM activity. analysis identified an optimal sequence with central core motif LSQE is preferentially phosphorylated by ATM. contributions amino acids surrounding serine were assessed utilizing specific libraries or individual substrates. All...
Inherited mutations in the ATM gene lead to a complex clinical phenotype characterized by neuronal degeneration, oculocutaneous telangiectasias, immune dysfunction, and cancer predisposition. Using yeast two-hybrid system, we demonstrate that ataxia telangiectasia mutated (ATM) binds β-adaptin, one of components AP-2 adaptor complex, which is involved clathrin-mediated endocytosis receptors. The interaction between β-adaptin was confirmed vitro, coimmunoprecipitation colocalization studies...
The product of the ataxia-telangiectasia gene (ATM) was identified by using an antiserum developed to a peptide corresponding deduced amino acid sequence. ATM protein is single, high-molecular weight predominantly confined nucleus human fibroblasts, but present in both nuclear and microsomal fractions from lymphoblast cells peripheral blood lymphocytes. levels localization remain constant throughout all stages cell cycle. Truncated not detected lymphoblasts patients homozygous for mutations...
ATM mutations are responsible for the genetic disease ataxia-telangiectasia (A-T).ATM encodes a protein kinase that is activated by ionizing radiation-induced double strand DNA breaks. Cells derived from A-T patients show many abnormalities, including accelerated telomere loss and hypersensitivity to radiation; they enter into mitosis apoptosis after damage. Pin2 was originally identified as involved in G2/M regulation almost identical TRF1, telomeric negatively regulates elongation....
The DNA damage response (DDR) is a complex signaling network that leads to repair while modulating numerous cellular processes. double-strand breaks (DSBs), highly cytotoxic lesion, activate this system most vigorously. DSB orchestrated by the ATM protein kinase, which phosphorylates key players in its various branches. Proteasome-mediated degradation plays an important role proteome dynamics following induction. Here, we identify nuclear proteasome activator PA28γ (REGγ; PSME3) as novel DDR...
Abstract Background Characterizing gut factors that improve or persist during Crohn’s disease (CD) trajectory from active to remission healthy-normal states is crucial for defining treatment targets and CD cure. Methods Using multi-omics (ileal transcriptomics, microbiome, metabolomics), we aimed compare active, mostly naïve newly diagnosed patients in remission, using controls as a reference Results 193 subjects were included (median age 32 years, 60% male); 78 38 (80%) patients, 77 non-IBD...