Huff, Laura A. and Yan, Shan and Clemens, Mark G. (2021) Mechanisms of Ataxia Telangiectasia Mutated (ATM) Control in the DNA Damage Response to Oxidative Stress, Epigenetic Regulation, and Persistent Innate Immune Suppression Following Sepsis. Antioxidants, 10 (7). p. 1146. ISSN 2076-3921
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Abstract
Cells have evolved extensive signaling mechanisms to maintain redox homeostasis. While basal levels of oxidants are critical for normal signaling, a tipping point is reached when the level of oxidant species exceed cellular antioxidant capabilities. Myriad pathological conditions are characterized by elevated oxidative stress, which can cause alterations in cellular operations and damage to cellular components including nucleic acids. Maintenance of nuclear chromatin are critically important for host survival and eukaryotic organisms possess an elaborately orchestrated response to initiate repair of such DNA damage. Recent evidence indicates links between the cellular antioxidant response, the DNA damage response (DDR), and the epigenetic status of the cell under conditions of elevated oxidative stress. In this emerging model, the cellular response to excessive oxidants may include redox sensors that regulate both the DDR and an orchestrated change to the epigenome in a tightly controlled program that both protects and regulates the nuclear genome. Herein we use sepsis as a model of an inflammatory pathophysiological condition that results in elevated oxidative stress, upregulation of the DDR, and epigenetic reprogramming of hematopoietic stem cells (HSCs) to discuss new evidence for interplay between the antioxidant response, the DNA damage response, and epigenetic status.
Item Type: | Article |
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Subjects: | Science Repository > Biological Science |
Depositing User: | Managing Editor |
Date Deposited: | 03 Oct 2023 12:51 |
Last Modified: | 03 Oct 2023 12:51 |
URI: | http://research.manuscritpub.com/id/eprint/2712 |