Clusters of Damage in Irradiated DNA
EMSL Project ID
19825
Abstract
This EMSL project will increase our knowledge of the spatial characteristics of the free radical damage at the interface between the physical deposition of energy in DNA from gamma irradiation and the complex of metalloproteins and repair enzymes that process this damage as part of the biological response to radiation. There is little experimental information on the spatial properties of these free radicals and yet these properties are very important in determining the efficiency and fidelity of the metalloprotein-DNA interactions that lead to repair, mis-repair or lack of repair of the DNA damage. For example, in clusters of radiation damaged DNA sites, the metalloprotein repair enzymes that are supposed to deal with this damage may not recognize the damage or form an effective repair complex. On the other hand at isolated damage sites that are separated by large distances, the repair may be efficient and normal. Spatial information is needed in order to develop a better understanding of the mechanisms involved when radiation produces damage and metalloprotein repair enzymes attempt to remove this damage and restore the DNA to its normal state. Models incorporating the data from this project will be more accurate in their prediction of risks for such adverse health effects as cancer from exposure to low doses of radiation or from exposure to different types of radiation such as gamma rays or transuranic waste. The results of these studies support DOE programs responsible for energy production, nuclear waste, radiation safety and worker health, as well as response to radiological terrorism. The specific aim of the project is to measure the dimensions of clusters of damaged DNA sites which include free radical intermediates, and the average number of free radicals in each cluster. Variables to be studied include radiation dose, DNA base sequence, packing and hydration.
The approach is to use pulsed electron paramagnetic resonance spectroscopy (EPR) methodologies developed at EMSL to study the magnetic interactions between trapped free radicals in DNA irradiated with gamma rays. Previous studies at EMSL on DNA irradiated with high energy particles shows that with the appropriate pulsing sequences and available theory, the EPR data allow important spatial information to be obtained.
Project Details
Project type
Large-Scale EMSL Research
Start Date
2006-08-17
End Date
2008-12-02
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members