So they are making large quantities of Ku which also is plentiful in people in the lab for study. As soon as Ku lays the framework, another protein, a large one called DNA-dependent protein kinase catalytic subunit, comes in to modify other proteins and bring in phosphates that are a cheap, easy way to turn proteins off and on, Dr. Dynan said. In the lab, they have used drugs that inhibit the kinase, which stops the transfer of phosphates and so halts the repair. After the ligase is done, the DNA is just like it was when it started. It s important and interesting to reconstruct the guardian of the genome in the test tube in order to understand how it works to help maintain a healthy body and because of its implications in cancer and cancer treatment, Dr. Dynan said.
People think failed attempts at repair are very important in why radiation produces cancer.
It s kind of a cycle of instability that can arise from an incorrect repair. On the flip side, understanding how the repair system works correctly, opens the potential for manipulating the system for example, turning it off in cancer cells to improve the effectiveness of radiation. MCG researchers also are exploring other potential roles of the key protein Ku in aging and autoimmune disease. Xingwen Dong and Kyungiong Lee, researchers in Dr. Dynan s group, more recently found that a small percentage of people with autoimmune disease also make antibodies to ligase, the enzyme that puts the finishing touches on DNA repair. Dr. Joseph P. Bailey Jr., a 1955 graduate of the MCG School of Medicine who recently retired as chief of the Section of Rheumatology, provided key study samples.