DNA Repair Protein OGG1 in Pulmonary Infection and Other Inflammatory Lung Diseases

In the last decades, extensive research has uncovered functional roles and underlying mechanisms of DNA repair enzyme 8-oxoguanine DNA glycosylase (OGG1) in the pathogenesis of inflammatory response in infection and other diseases in the lung. OGG1 excises 8-oxo-7,8-dihydroguanine (8-oxo-dG) lesion on DNA that is often induced by generation of reactive oxygen species (ROS) and has been linked to mutations, cancer development, and tissue damage. Most, if not all, environmental toxic agents and mammalian cellular metabolites elicit the generation of ROS, either directly, indirectly, or both, which is among the first cellular responses. ROS in combination with other oxidative molecules/moieties are recognized as a major factor for killing invading pathogens but meanwhile can cause tissue damage. ROS potentially modify proteins, lipids, and DNA due to the strong molecular reactivity. While oxidative stress causes increased levels of all types of oxidatively modified DNA bases, accumulation of 8-oxo-dG in the DNA has been singled out to be a main culprit linking to various inflammatory disease processes. Oxidatively damaged DNA bases such as 8-oxo-dG are primarily repaired by the base excision repair (BER) mechanism, in which OGG1, as the lesion recognition enzyme, plays a fundamental role in fixing this DNA damage. In this chapter, we summarize the roles and potential mechanistic analyses of OGG1 in lung infection and other inflammatory diseases.