Schematic of different mechanisms of DNA damage.

Ionizing radiation, chemicals, and other agents can result in genetic damage, which, if not repaired, can lead to diseases such as cancer. Fortunately, a system of genes directs the production of sensitive DNA repair enzymes, which monitor for genetic damage and fix most errors. The role of DNA repair processes in fixing genetic damage, as well as the role of genetically impaired repair mechanisms in cancer, were first discovered by investigators funded by predecessors to the Office of Science in the 1960s. More recently at Lawrence Livermore, Los Alamos, and Lawrence Berkeley national laboratories, researchers have cloned and studied a number of crucial DNA repair genes. A clear picture is emerging that unrepaired DNA damage is the culprit in the long-term consequences of radiation exposure. Scientists now see that X-rays, ultraviolet light, and cancer-causing chemicals work in similar ways in disabling the natural DNA repair mechanisms. A team at Lawrence Berkeley demonstrated a strong correlation between the inability to repair oxidative damage to DNA and severe developmental failure and early death in a hereditary condition called Cockayne's syndrome.

Scientific Impact: Research on DNA repair helps scientists better understand biological processes, from the microscale (e.g., cell death) to the macroscale (e.g., evolution). So central is the role of DNA repair that in 1994, Science magazine designated the entire class of DNA repair enzymes as "Molecule of the Year."

Social Impact: By explaining how DNA repair processes can go awry, scientists contribute to sound policymaking on environmental hazards. This research also could lead to medical and pharmaceutical treatments for repair-deficiency disorders, implicated in conditions ranging from cancer to aging.

Reference: R.D. Wood, M. Mitchell, J. Sgouros, T. Lindahl, "Human DNA Repair Genes," Science 291 (2001) 1284-1289.

L.H. Thompson, D. Schild, "The contribution of homologous recombination in preserving genome integrity in mammalian cells," Biochimie (1999) 87-105.

M. Takata, M.S. Sasaki, S. Tachiiri, T. Fukushima, E. Sonoda, D. Schild, L.H. Thompson, S. Takeda, "Chromosome instability and defective recombinational repair in knockout mutants of the five Rad51 paralogs," Mol. Cell. Biol. 21 (2001) 2858-2866.

Le Page, F., Kwoh, E.E., Avrutskaya, A., Gentil, A., Leadon, S.A., Sarasin, A., and Cooper, P.K. "Transcription-Coupled Repair of 8-oxoGuanine: Requirement for XPG, TFIIH, and CSB and Implications for Cockayne Syndrome," Cell 101, 159-171 (2000).

Brenneman, M. A., A. E. Weiss, J. A. Nickoloff and D. J. Chen, "XRCC3 is Required for efficient repair of chromosome break by homologous recombination," DNA Repair Mutat Res 20;459(2):89-97 (2000).

URL: http://dir.niehs.nih.gov/dirlmg/DNArepair.html

Technical Contact: Dr. David Thomassen, Life Sciences Division, Office of Biological and Environmental Research, 301-903-9817

Press Contact: Jeff Sherwood, DOE Office of Public Affairs, 202-586-5806

SC-Funding Office: Office of Biological and Environmental Research