Key Step Discovered in DNA Damage from Oxidative Stress

Humans need energy to function and yet a naturally occurring process that generates power for the body can also harm its cells. Cellular mitochondria produce energy, as well as molecules known as reactive oxygen species (ROS). Through a process called oxidative stress, ROS harm cellular DNA by producing frayed ends that cannot be properly fixed during DNA repair processes. The presence of broken DNA will trigger the cell to self-destruct. This is one way the body preserves DNA integrity.

Based on work done by research fellow Dr. Melike Caglayan, a team led by Dr. Sam Wilson reported in Nature Communications how the damage from oxidative stress leads to DNA strand breaks, and ultimately, cell death. Using biochemical and cell biology methods, along with X-ray crystallography, the scientists demonstrated a subtle way that cells can accommodate the damage inflicted by ROS.

The killing power of ROS is important for the process known as innate immunity, or the natural immunity a person is born with. When a bacterium enters the body, a white blood cell activates an immune cell called a macrophage, which douses the bacterium with ROS. Just as ROS causes breaks in human cellular and mitochondrial DNA, it also breaks the bacterium’s DNA, thus killing it. The scheme is a resourceful way to kill living things that could make a person sick, but the ROS response is also triggered when the invaders are particles, such as those in cigarette smoke or smog. In human lung cells, the process may eventually lead to fibrosis, or the thickening or scarring of tissue. Oxidative stress is also linked to chronic lung disease, cataracts, cardiovascular disease and some neurodegenerative disorders. The scientists hope the new findings will lead to better understanding of the origins of these diseases.