(250e) Molecular Dynamics Simulation Study of DNA Damage Recognition

DNA damage can be in the form of base damage such as oxidation, methylation, dimerization, or strand damage such as single or double strand breaks. Diminished capacity of the cells to repair DNA damage is linked to high rates of cancer and other neurodegenerative diseases. Interestingly, anti-cancer drugs are also designed to damage the DNA in order to inhibit continuous cell growth. But increased repair of drug-induced DNA damage that does not end in cell death (apoptosis) can lead to tumor resistance to that drug. It is thus important to develop a better understanding of how DNA damage is recognized and repaired, not only to prevent malignancy, but also to avoid development of tumor resistance to current cancer therapies. In this talk we will present atomistic molecular dynamics simulation results that show the effects of oxidized base damage, specifically guanine damage, on DNA and the implications of these structural and thermodynamic effects on the ability of repair proteins to distinguish and recognize one type of base damage better than the other.