个人简介

ACS Fellow (2011) AAAS Fellow (2010) AP Sloan Fellow Beckman Young Investigator Appointed to UC Davis faculty (2006) NIH Postdoctoral Fellow, California Institute of Technology (1990-92) Ph.D. University of Minnesota (1989) B.A. Saint Olaf College (1984)

研究领域

Bioinorganic Chemistry/Chemical Biology/Organic Chemistry

We use chemical approaches to investigate the fascinating area of DNA repair. Damage to DNA can result in deleterious outcomes, such as cancer and aging; fortunately, most DNA damage is repaired by DNA repair enzymes. Our laboratory focuses on the repair of damaged DNA bases which is mediated by the process of base excision repair. The key enzymes in this pathway are the damage-specific DNA glycosylases that search through the vast amount of normal DNA to find subtle potentially mutagenic base modifications. Our goals are to understand the molecular details associated with the recognition and repair of DNA damage, and how these features impact mutagenesis and carcinogenesis. As chemical biologists interested in DNA repair, we use a variety of approaches, including enzymology, synthesis of modified substrates, spectroscopy, and cell biology. Importantly, putting these approaches together in unique ways allows connections to be made between the molecular insight derived from our in vitro studies, and how these features impact repair in cells. Ultimately this will reveal the critical features of the DNA repair process that prevents deleterious mutations leading to cancer, and how these processes may be manipulated for beneficial therapeutic purposes.

近期论文

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"A Zinc Linchpin Motif in the MUTYH Glycosylase Interdomain Connector Is Required for Efficient Repair of DNA Damage." Engstrom LM, Brinkmeyer MK, Ha Y, Raetz AG, Hedman B, Hodgson KO, Solomon EI, David SS. J Am Chem Soc. 2014 May 23. "Repair of hydantoin lesions and their amine adducts in DNA by base and nucleotide excision repair." McKibbin PL, Fleming AM, Towheed MA, Van Houten B, Burrows CJ, David SS. J Am Chem Soc. 2013 Sep 18. "Cancer-associated variants and a common polymorphism of MUTYH exhibit reduced repair of oxidative DNA damage using a GFP-based assay in mammalian cells." Raetz AG, Xie Y, Kundu S, Brinkmeyer MK, Chang C, David SS. Carcinogenesis. 2012 Aug 26. "NEIL1 binding to DNA containing 2'-fluorothymidine glycol stereoisomers and the effect of editing." Onizuka K, Yeo J, David SS, Beal PA. Chembiochem. 2012 Jun 18;13(9):1338-48. "An iron-sulfur cluster loop motif in the Archaeoglobus fulgidus uracil-DNA glycosylase mediates efficient uracil recognition and removal. " Engstrom LM, Partington OA, David SS. Biochemistry. 2012 Jun 26;51(25):5187-97. "Catalytic contributions of key residues in the adenine glycosylase MutY revealed by pH-dependent kinetics and cellular repair assays." Brinkmeyer MK, Pope MA, David SS. Chem Biol. 2012 Feb 24;19(2):276-86. "Direct Fluorescence Monitoring of DNA Base Excision Repair" Ono T, Wang S, Koo CK, Engstrom L, David SS, Kool ET. Angew Chem Int Ed Engl. 2012 Jan 12. "Surprising Repair Activities of Nonpolar Analogs of 8-oxoG Expose Features of Recognition and Catalysis by Base Excision Repair Glycosylases" McKibbin PL, Kobori A, Taniguchi Y, Kool ET, David SS. J Am Chem Soc. 2012 Jan 25;134(3):1653-61. "Profiling base excision repair glycosylases with synthesized transition state analogs" Chu AM, Fettinger JC, David SS. Bioorg Med Chem Lett. 2011 Sep 1;21(17):4969-72. "RNA editing changes the lesion specificity for the DNA repair enzyme NEIL1" Yeo J, Goodman RA, Schirle NT, David SS, Beal PA. Proc Natl Acad Sci U S A. 2010 Nov 30;107(48):20715-9. "Ser 524 is a phosphorylation site in MUTYH and Ser 524 mutations alter 8-oxoguanine (OG): a mismatch recognition" Kundu S, Brinkmeyer MK, Eigenheer RA, David SS. DNA Repair (Amst). 2010 Oct 5;9(10):1026-37. "Mutation versus Repair: NEIL1 Removal of Hydantoin Lesions in Single-Stranded, Bulge, Bubble, and Duplex DNA Contexts" Zhao X, Krishnamurthy N, Burrows CJ, David SS. Biochemistry. 2010 Mar 2;49(8):1658-66. "Adenine removal activity and bacterial complementation with the human MutY homologue (MUTYH) and Y165C, G382D, P391L and Q324R variants associated with colorectal cancer" Kundu S, Brinkmeyer MK, Livingston AL, David SS. DNA Repair (Amst). 2009 Oct 14. "Superior removal of hydantoin lesions relative to other oxidized bases by the human DNA glycosylase hNEIL1." Krishnamurthy N, Zhao X, Burrows CJ, David SS. Biochemistry. 2008 Jul 8;47(27):7137-46. "Inorganic chemical biology: from small metal complexes in biological systems to metalloproteins" David SS, Meggers E. Curr Opin Chem Biol. 2008 Apr;12(2):194-6. "Efficient removal of formamidopyrimidines by 8-oxoguanine glycosylases" Krishnamurthy N, Haraguchi K, Greenberg MM, David SS. Biochemistry. 2008 Jan 22;47(3):1043-50. Epub 2007 Dec 23. "Unnatural substrates reveal the importance of 8-oxoguanine for in vivo mismatch repair by MutY" Livingston AL, O'Shea VL, Kim T, Kool ET, David SS. Nat Chem Biol. 2008 Jan;4(1):51-8. "Base-excision repair of oxidative DNA damage" David, S. S., O'Shea, V.L., Kundu, S., Nature, 2007, 447(7147),941-50. "Unusual Structural Features of Hydantoin Lesions Translate into Efficient Recognition by Escherichia coli Fpg." Biochemistry, 2007, 21;46(33),9355-65. "An Electron Trap for DNA-bound Repair Enzymes: A Strategy for DNA-mediated Signaling" Yavin, E., Stemp, E.D.A., O'Shea, V.L., David, S. S., Barton, J.K., Proc. Natl. Acad. Sci, USA, 2006, 103, 3610-3614.