title: New insights into the roles of ATM and DNA-PKcs in the cellular response to oxidative stress.
abstract: Reactive oxygen species (ROS) are induced by a variety of endogenous and exogenous sources. At pathologically high levels, ROS cause damage to biological molecules, including DNA. The damage sustained by DNA likely plays a key role in the pathogenesis of aging and carcinogenesis. Extensive research has established in detail the mechanism of cellular response to oxidative stress. Attention is now focused on identifying the molecular contributions of the key DNA damage response kinases ataxia telangiectasia mutated (ATM), DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and ATM- and Rad3-related (ATR) in the oxidative stress response. In this review, we will provide an update of the current evidence regarding the involvement of these related DNA damage response kinases in oxidative DNA lesion repair and signaling responses. The growing understanding of the involvement of ATM, DNA-PKcs, and ATR in the oxidative stress response will offer new possibilities for the treatment of ROS-related diseases.
authors.affiliation: Department of Radiation Oncology/Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center at Dallas, 75390-9187, USA. benjamin.chen@utsouthwestern.edu
authors.forename: Benjamin P C
authors.initials: BP
authors.lastname: Chen
authors.forename: Mengxia
authors.initials: M
authors.lastname: Li
authors.forename: Aroumougame
authors.initials: A
authors.lastname: Asaithamby
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004261:DNA Replication; D051747:DNA-Activated Protein Kinase / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases