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The Impact of DNA Damage on Epithelial Cell Maintenance of the Lung

  • Lidza Kalifa
  • Michael A. O’ReillyEmail author
Chapter
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Part of the Respiratory Medicine book series (RM, volume 15)

Abstract

The primary function of the lung is to facilitate the exchange of oxygen and carbon dioxide between air and blood and to exclude or defend against infectious agents and other airborne pollutants. As such, the respiratory epithelium is under constant attack by reactive oxygen species derived from metabolic respiration and the inflammatory response to pathogens in the airway. While reactive oxygen species can damage all macromolecules, oxidative damage to DNA is of great importance because it can affect how cells and hence organs function. DNA lesions activate a family of phosphatidylinositol-3 kinase-related kinases (PIKKs) that phosphorylate numerous substrates, including the tumor suppressor p53, which is critically important for maintaining genome integrity. While oxidized DNA is historically thought to be detrimental to cell function, emerging evidence suggest that it may also be an important post-replication modification that controls gene expression. Understanding how oxidation of nuclear and mitochondrial DNA affects cell function could provide new opportunities for treating lung diseases attributed to oxidant injury to the respiratory epithelium.

Keywords

Reactive oxygen species DNA damage Mitochondria Nucleus Cell signaling 
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Notes

Acknowledgements

The authors’ research is supported in part by National Institutes of Health grants HL067392, HL091968, and HL097141 to M. O’Reilly and NIH Training Grant ES07026 to L. Kalifa.

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of PediatricsSchool of Medicine and Dentistry, The University of RochesterRochesterUSA

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