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Low Temperature (10K) 25Mg Solid-State NMR of DNA Repair Proteins and Their
Complexes


EMSL Project ID
24991

Abstract

The chemistry central to the function of the DNA repair proteins apurinic/apyrimidic endonuclease 1 (APE1) and polymerase β (Pol β) is the chemistry of water activated by Mg2+. These proteins are key constituents of the base excision repair (BER) pathway, a process that plays a critical role in preventing the cytotoxic and mutagenic effects of most spontaneous, alkylation and oxidative DNA damage. The principal aim of the proposed research is to establish a relationship between 25Mg magnetic resonance parameters and the structure/function relationships for known Mg-dependent DNA repair proteins and extrapolating those relationships to DNA repair proteins where the role of the magnesium is less defined. This work is in collaboration with S. Wilson (Pol β - NIEHS) and D. Wilson III (APE1 -NIA). Due to the similarity of the questions and the proposed science, we have combined these efforts.

Project Details

Project type
Large-Scale EMSL Research
Start Date
2007-05-23
End Date
2010-09-30
Status
Closed

Team

Principal Investigator

Paul Ellis
Institution
Pacific Northwest National Laboratory

Team Members

Priscilla Moore
Institution
Pacific Northwest National Laboratory

Robert Heck
Institution
Pacific Northwest National Laboratory

Samuel Wilson
Institution
National Institute of Environmental Health Sciences, NIH

David Wilson
Institution
Hasselt University

Andrew Lipton
Institution
Environmental Molecular Sciences Laboratory

Marat Valiev
Institution
Environmental Molecular Sciences Laboratory

Related Publications

Lipton AS, PD Ellis, and TE Polenova. 2009. "Quadrupolar Metal Nuclides in Bioinorganic Chemistry: Solid-State NMR Studies." In Encyclopedia of Magnetic Resonance. John Wiley & Sons, Ltd., Hoboken, NJ.
Lipton AS, RW Heck, SV Primak, DR McNeill, DM Wilson Iii, and PD Ellis. 2008. "Characterization of Mg2+ Binding to the DNA Repair Protein Apurinic/Apyrimidic Endonuclease 1 via Solid-State 25Mg NMR Spectroscopy." Journal of the American Chemical Society 130(29):9332-9341. doi:10.1021/ja0776881