A5065867383- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Carcinogens and Genotoxicity Assessment
- CRISPR and Genetic Engineering
- PARP inhibition in cancer therapy
- Mitochondrial Function and Pathology
- Ubiquitin and proteasome pathways
- RNA modifications and cancer
- Ecology and Conservation Studies
- Agriculture, Soil, Plant Science
- Genomics and Chromatin Dynamics
- Protein Degradation and Inhibitors
- Microtubule and mitosis dynamics
- Plant Molecular Biology Research
- DNA and Nucleic Acid Chemistry
- Lung Cancer Treatments and Mutations
- Genetic Neurodegenerative Diseases
- Epigenetics and DNA Methylation
- Endoplasmic Reticulum Stress and Disease
- Photosynthetic Processes and Mechanisms
- RNA Research and Splicing
- Chromosomal and Genetic Variations
- Neurobiology and Insect Physiology Research
- Acute Lymphoblastic Leukemia research
- Plant nutrient uptake and metabolism
The University of Texas Health Science Center at San Antonio
2025
Chonnam National University
2023-2025
Jeonbuk National University
2021-2024
The University of Texas at Austin
2009-2021
Howard Hughes Medical Institute
2010-2019
Kyung Hee University
2017
Seoul National University
2013-2015
Keimyung University
2012-2013
Advanced Institute of Convergence Technology
2013
University of Ottawa
2013
The ataxia-telangiectasia mutated (ATM) kinase signals the presence of DNA double-strand breaks in mammalian cells by phosphorylating proteins that initiate cell-cycle arrest, apoptosis, and repair. We show Mre11-Rad50-Nbs1 (MRN) complex acts as a break sensor for ATM recruits to broken molecules. Inactive dimers were activated vitro with MRN, leading phosphorylation downstream cellular targets p53 Chk2. autophosphorylation was not required monomerization MRN. unwinding ends MRN essential...
The complex containing the Mre11, Rad50, and Nbs1 proteins (MRN) is essential for cellular response to DNA double-strand breaks, integrating repair with activation of checkpoint signaling through protein kinase ATM (ataxia telangiectasia mutated). We demonstrate that MRN stimulates activity in vitro toward its substrates p53, Chk2, histone H2AX. makes multiple contacts appears stimulate by facilitating stable binding substrates. Phosphorylation critical stimulation but not p53....
Double-strand breaks (DSBs) in chromosomal DNA elicit a rapid signaling response through the ATM protein kinase. Recent evidence suggests that repair complex containing Mre11, Rad50 and Nbs1 (MRN) is important for activation of by DSBs cells. Our studies effects MRN on activity vitro indicated stimulates multiple protein-protein contacts, this interaction increases affinity its substrates. Recently we isolated dimeric forms ATM, which require but also DNA, similar to requirements vivo. Here...
Abstract All cells have intricately coupled sensing and signaling mechanisms that regulate the cellular outcome following exposure to genotoxic agents such as ionizing radiation (IR). In IR-induced pathway, specific protein events, ataxia-telangiectasia mutated (ATM) activation histone H2AX phosphorylation (γ-H2AX), are mechanistically well characterized. How these can be altered, especially by clinically relevant agents, is not clear. Here we show hyperthermia, an effective radiosensitizer,...
The functions of long noncoding RNAs (lncRNAs) have been identified in several cancers, but the roles lncRNAs colorectal cancer (CRC) are less well understood. transcription factor MYC is known to regulate and has implicated cell proliferation tumorigenesis.CRC cells tissues were profiled identify differentially expressed CRC, from which we further selected MYC-regulated lncRNAs. We used luciferase promoter assay, ChIP, RNA pull-down deletion mapping LC-MS/MS immunoprecipitation determine...
Abstract Purpose: Common treatment modalities for non–small cell lung cancer (NSCLC) involve the EGF receptor-tyrosine kinase inhibitors (EGFR-TKIs) like gefitinib and erlotinib. However, vast majority of treated patients acquire resistance to EGFR-TKIs, due, in large part, secondary mutations EGFR or amplification MET gene. Our purpose was test ubiquitin-specific peptidase 8 (USP8) as a potential therapeutic target gefitinib-resistant -sensitive (NSCLC). Experimental Design: Testing effect...
Independent functions in the response to DNA damage and oxidative stress broaden biological roles of kinase ATM.
The kinase ATM stimulates antioxidant metabolism to prevent oxidative stress in cells.
Cellular responses to both physiological and pathological DNA double-strand breaks are initiated through activation of the evolutionarily conserved ataxia telangiectasia mutated (ATM) kinase. Upon damage, an mechanism involving autophosphorylation has been reported allow ATM phosphorylate downstream targets important for cell cycle checkpoints repair. In humans, serine residues 367, 1893, 1981 have shown be sites that individually required activation. To test importance these sites, we...
The Mre11/Rad50/NBN complex plays a central role in coordinating the cellular response to DNA double-strand breaks. importance of Rad50 that is evident from recent description patient with deficiency characterized by chromosomal instability and defective ATM-dependent signaling. We report here ATM (defective ataxia-telangiectasia) phosphorylates at single site (Ser-635) an important adaptor signaling for cell cycle control repair. Although phosphosite-specific mutant (S635G) supported normal...
The Sae2/CtIP protein is required for efficient processing of DNA double-strand breaks that initiate homologous recombination in eukaryotic cells. also important survival single-stranded Top1-induced lesions and CtIP known to associate directly with transcription-associated complexes mammalian Here we investigate the role at single-strand budding yeast human cells find depletion promotes accumulation stalled RNA polymerase RNA-DNA hybrids sites highly expressed genes. Overexpression helicase...
The 70 kDa heat shock protein (HSP70) family of chaperones are the front line protection from stress-induced misfolding and aggregation polypeptides in most organisms responsible for promoting stability, folding, degradation clients to maintain cellular homeostasis. Here, we demonstrate quantitative identification HSP70 71 cognate (HSC70) using a ubiquitin-mediated proximity tagging strategy show that, despite their high degree similarity, these enzymes have largely nonoverlapping...