کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8270001 | 1534966 | 2014 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The catalytic subunit of DNA-dependent protein kinase is required for cellular resistance to oxidative stress independent of DNA double-strand break repair
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کلمات کلیدی
HSCAtaxia telangiectasiaMRNHIF-1αECLN-acetyl-l-cysteineBERH2DCF-DAHDACNHEJNACDNA-PKcsAPE1A-TMre11-Rad50-Nbs1DSBapurinic/apyrimidinic endonuclease - apurinic / apyrimidinic endonucleaseataxia telangiectasia mutated - Ataxia telangiectasia جهش یافته استPIKK - LIKKO2− - O2-Hydrogen peroxide - آب اکسیژنهenhanced chemiluminescence - بهبود شیمیایی لومنionizing radiation - تابش یوننده یا پرتوهای یونیزانbase excision repair - تعمیر پایه پایهATM - خودپردازdichlorodihydrofluorescein diacetate - دی کلستیدوفروفوروزین دی سکتهSuperoxide anion radical - رادیکال آنیون سوپراکسیدHydroxyl radical - رادیکال هیدروکسیلHematopoietic stem cell - سلول بنیادی هماتوپوئیتDNA double-strand break - شکست دو رشته DNAhypoxia-inducible factor-1α - عامل القاء شده با هیپوکسی 1αH2O2 - هیدروژن پراکسیدHydroxyurea - هیدروکسی اورهhistone deacetylase - هیستون داستیلازDNA-dependent protein kinase catalytic subunit - وابسته به DNA وابسته به پروتئین کیناز کاتالیزوریNonhomologous end-joining - پیوستن به انتهای غیرخطیFanconi anemia - کم خونی Fanconi
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
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چکیده انگلیسی
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated (ATM) are the two major kinases involved in DNA double-strand break (DSB) repair, and are required for cellular resistance to ionizing radiation. Whereas ATM is the key upstream kinase for DSB signaling, DNA-PKcs is primarily involved in DSB repair through the nonhomologous end-joining (NHEJ) mechanism. In addition to DSB repair, ATM has been shown to be involved in the oxidative stress response and could be activated directly in vitro on hydrogen peroxide (H2O2) treatment. However, the role of DNA-PKcs in cellular response to oxidative stress is not clear. We hypothesize that DNA-PKcs may participate in the regulation of ATM activation in response to oxidative stress, and that this regulatory role is independent of its role in DNA double-strand break repair. Our findings reveal that H2O2 induces hyperactivation of ATM signaling in DNA-PKcs-deficient, but not Ligase 4-deficient cells, suggesting an NHEJ-independent role for DNA-PKcs. Furthermore, DNA-PKcs deficiency leads to the elevation of reactive oxygen species (ROS) production, and to a decrease in cellular survival against H2O2. For the first time, our results reveal that DNA-PKcs plays a noncanonical role in the cellular response to oxidative stress, which is independent from its role in NHEJ. In addition, DNA-PKcs is a critical regulator of the oxidative stress response and contributes to the maintenance of redox homeostasis. Our findings reveal that DNA-PKcs is required for cellular resistance to oxidative stress and suppression of ROS buildup independently of its function in DSB repair.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 76, November 2014, Pages 278-285
Journal: Free Radical Biology and Medicine - Volume 76, November 2014, Pages 278-285
نویسندگان
Mengxia Li, Yu-Fen Lin, Guillermo A. Palchik, Shinji Matsunaga, Dong Wang, Benjamin P.C. Chen,