Department of Radiation Oncology/Division of Molecular Radiation Biology, University of Texas Southwestern Medical Center at Dallas, 75390-9187, USA.
Cancer Lett. 2012 Dec 31;327(1-2):103-10. doi: 10.1016/j.canlet.2011.12.004. Epub 2011 Dec 9.
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.
活性氧 (ROS) 由多种内源性和外源性来源诱导。在病理性高水平下，ROS 会对包括 DNA 在内的生物分子造成损伤。DNA 所承受的损伤可能在衰老和致癌作用的发病机制中发挥关键作用。大量研究详细阐明了细胞对氧化应激的反应机制。目前的研究重点是确定关键 DNA 损伤反应激酶共济失调毛细血管扩张突变 (ATM)、DNA 依赖性蛋白激酶催化亚基 (DNA-PKcs) 和 ATM 和 Rad3 相关 (ATR) 在氧化应激反应中的分子贡献。在这篇综述中，我们将提供有关这些相关 DNA 损伤反应激酶在氧化 DNA 损伤修复和信号反应中的作用的最新证据。对 ATM、DNA-PKcs 和 ATR 参与氧化应激反应的认识不断加深，为治疗与 ROS 相关的疾病提供了新的可能性。
