Chapter 273 - Stress and γ-H2AX

Abstract

This chapter discusses the concept of stresses that may induce DSB formation, the mechanisms of various cellular responses, and methods of DSB detection. Stress occurs when a cell or organism is subjected to a non-optimal environment leading to cell death or cellular damage. One type of genomic damage that is a serious threat to cell health is the DNA double-stranded break (DSB) because of its propensity to induce irreversible genomic rearrangements, which, if not fatal, may promote cellular oncogenesis. However, even in an optimum environment, DSBs can originate as part of normal cellular processes. One potential damage source is the presence of reactive oxygen species (ROS) in cells. Mutations in DNA damage repair proteins result in DSBs and elevated γ-H2AX formation, leading to genomic instability and cancer. DSBs may arise from a variety of exogenous chemical/physical sources, such as ionizing radiation (IR), radioactive isotopes, and cosmic radiation, or by non-ionizing radiation. To combat threats to genome integrity, living systems have evolved a highly regulated, intricate system of repair pathways. The DNA damage response (DDR) machinery helps maintain the health of the cell population and prevent cancer. A key protein in the DDR machinery is histone H2AX, which is one of the most rapid and sensitive cellular responses to DNA damage. Therefore the detection of γ-H2AX is a very powerful tool to monitor the effects of stress in the cellular environment.