DNA Ligase IV Gene and Radiation Sensitivity
Human cells have several mechanisms to deal with DNA damage. The proper functioning of proteins involved in this genome maintenance repairs mutations that might cause cells to become cancerous or prevents their proliferation if they do. Previous studies indicate that ATM, the gene mutated in the recessive disorder Ataxia telangiectasia, serves as a sensor of double strand breaks in DNA caused by ionizing radiation. Other genes act downstream of ATM and carry out DNA repair. One such gene, DNA ligase IV, has recently been found to be mutated in patients who are sensitive to radiation.
In the Concannon Lab I will be working with the genomic DNA from 37 cancer patients who all had adverse reactions to radiation therapy to determine whether their DNA ligase IV gene is mutated. I will define conditions for detection of mutations by denaturing high pressure liquid chromatography (DHPLC). DHPLC is a very sensitive technique that can detect mutations in partially denatured DNA heteroduplexes. Developing tests for radiation sensitivity in cancer patients will protect them from complications from radiation therapy. This information is generally valuable because then health care providers will be able to employ different methods of therapy to optimize cancer patient treatments.
