Structural Studies of Escherichia coli formamidopyrimidine DNA N-glycosylase and its main biological substrate 8-oxoguanine
EMSL Project ID
1787a
Abstract
DNA repair plays a fundamental role in human health. Our genomic DNA is under constant assault by endogenous oxidative stress and by exogenous factors associated with our environment. Basic questions related to the processes of DNA damage recognition and repair remain unanswered. 8-Oxoguanine (8OG) is a stable product of oxidative DNA damage, and is a substrate for base excision repair (BER) by DNA glycosylases that recognize and remove the damaged base. In prokaryotes the BER enzyme formamidopyrimdine-DNA glycosylase (Fpg) removes 8OG but it is not understood how this enzyme recognizes and removes the lesion. One theory is that 8OG perturbs the phosphodiester backbone locally at the lesion site and Fpg recognizes this perturbation. A goal of our research is to understand how the structure and dynamics related to DNA damage is modulated by sequence context and how this in turn influences the sequence context dependent repair efficiency of 8OG by Fpg.
Project Details
Project type
Capability Research
Start Date
2003-04-01
End Date
2004-04-09
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
G.W. Buchko, K. McAteer, S.S. Wallace, and M.A. Kennedy. (2005) Solution-state NMR investigation of DNA binding interactions in Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg): A dynamic description of the DNA/protein interface. DNA Repair, 4:327-339.