Comparison between the Base Eversion of 8OG:C and G:C

TOXI 63

Arthur J. Campbell, ajcampbell@anchovy.org1, Arthur P. Grollman, apg@pharm.sunysb.edu2, and Carlos L. Simmerling, carlos.simmerling@sunysb.edu1. (1) Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, (2) Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794-8651
Oxidative DNA damage has been linked to a number of human diseases including cancer. The most common oxidative lesion found in DNA is 8-oxoguanine (8OG). Failure to repair this lesion prior to replication may lead to G:C to A:T transversion mutations in bacterial and mammalian cells. 8OG is present only in 1/106 nucleotides, raising the question as to how this lesion is located by its cognate repair enzyme in a vast sea of unmodified DNA. Lesion recognition may involve “indirect readout”, via detection of thermodynamic instability at the lesion site. To investigate “indirect readout” we use umbrella sampling to calculate the free energy profile of base eversion and directly compare the energy barrier of the normal G:C base pair to that of 8OG:C.
 

Poster Session and Awards
6:00 PM-10:00 PM, Tuesday, August 21, 2007 BCEC -- 204 A/B, Poster

Division of Chemical Toxicology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007