Overview of DNA Repair

Each cell (e.g. a liver, muscle, or brain cell) in our body contains information in the form of DNA (the genetic material) that determines our physical and biological traits. Through a carefully controlled process called gene expression, the information within the DNA is transmitted into protein molecules, which carry out most of our cellular operations. It is this genetic material that is faithfully copied (replicated) and passed on from generation to generation, perpetuating the features of the parent and providing children with the necessary information for existence. While some genetic variation must occur in order for us to adapt to environmental change and to develop distinguishing characteristics, radical or inappropriate modification of our genetic material can lead to the development of human disease. Thus, maintaining the overall integrity of our DNA is imperative.

Our genetic material is exposed to a number of physical and chemical agents, both environmental and intracellular, that introduce, either directly or indirectly, a wide range of DNA modifications (damage-repair figure). These agents include sunlight (ultraviolet radiation), X-rays, food mutagens, and reactive chemical species [e.g. oxygen free radicals that are formed as by-products of energy (ATP) production]. Our DNA being a chemical is also susceptible to spontaneous decay. Furthermore, errors can be introduced during DNA replication (i.e. the copying of our DNA) and imperfect exchanges (i.e. recombination) can take place between our chromosomes, the DNA elements that contain genetic information. In all, temporary modifications to DNA can lead to permanent changes in our genetic material. By inactivating or deregulating control proteins, such mutagenic events can have a detrimental effect on normal biological processes, leading to cell death or cellular dysfunction, and ultimately human disease, most notably cancer. Cancer is a normal cell that has lost the ability to regulate (i.e. stop) growth.

To cope with the harmful effects of DNA damage, organisms have evolved an elaborate array of repair systems that maintain genetic integrity (damage-repair figure). These systems must first recognize specific forms of DNA damage, remove this damage, and ultimately replace the aberrant segment with a normal piece of DNA. Such processes involve highly integrated pathways of several protein factors discussed in more detail in the tutorial. As research continues in the area of DNA repair, the known number and types of DNA damages, as well as the biological processes that are linked to repair and persevering genetic integrity, will continue to grow. The Biology Program at Lawrence Livermore National Laboratory is working to understand the mechanisms of DNA repair and to improve current methods of diagnosing and treating cancer.