Argonne National Laboratory

GM/CA @ APS

Users Highlights

Department of Energy Office of Science
GM/CA @ APS Sponsors:
National Institute of General Medical Sciences (NIGMS) and National Cancer Institute (NCI) of the National Institutes of Health (NIH)
 

Repair of oxidative damage to DNA

Sylvie Doublié group (University of Vermont)

 

The group of Sylvie Doubliť at the University of Vermont solved structures of two 8-oxoguanine DNA glycosylases, which recognize specific DNA lesions and initiate repair processes. Guanine is the most vulnerable of DNA bases to oxidative damage; its most common oxidative product, 7,8-dihydro-8-oxoguanine (8-oxoG), is the most prevalent defect found in DNA molecules. In the base-excision DNA repair pathway, 8-oxoG is recognized by 8-oxoguanine DNA glycoslyase (Ogg), which cleaves the N-glycosylic bond and then the DNA backbone. Ogg enzymes occur in three families: Ogg1, Ogg2, and AGOG. This work provides the first Ogg2 structures, from Methanocaldococcus janischii (MjaOgg) and Sulfolobus solfataricus (SsoOgg). The structures show that the C-terminal lysine of Ogg2 plays a key role in discriminating between guanine and 8-oxoG in Ogg2. Comparison with the structure of human Ogg1 shows some conserved features in the C-terminal region for binding 8-oxoG, as well as some key differences.

Figure: (A) Alignment of the C-terminal region of several Ogg2 sequences, showing the conserved "stacking" tryptophan and the C-terminal lysine (red). (B) Ribbon diagram showing a superposition of the C-terminal loop of MjaOgg (red), SsoOgg (yellow), the ?A-?B loop of human Ogg1 (gray) (PDB 1EBM), and CacOgg (green) (PDB 3F10). The superposition shows the importance of an aromatic stacking interaction (Trp198 in Ogg2) with the 8-oxoG substrate.

 

Citation:
Faucher, F, Duclos, S, Bandaru, V, Wallace, SS Doublié, S. Crystal Structures of Two Archaeal 8-Oxoguanine DNA Glycosylases Provide Structural Insight into Guanine/8-Oxoguanine Distinction, Structure 17 (5), 703-712 (2009). DOI: 10.1016/j.str.2009.03.007


GM/CA @ APS is an Office of Science User Facility operated for the U.S. Department of Energy Office of Science by Argonne National Laboratory

UChicago Argonne LLC | Privacy & Security Notice | Contact Us | A-Z Index | Search