Walter J. Chazin, Ph.D.

Chancellor's Professor of Biochemistry and Chemistry

Ingram Professor of Cancer Research

Director, Center for Structural Biology and Vanderbilt NMR Center

Ph.D., Concordia University, Montréal, Canada, 1983 (Physical Chemistry)

A major interest in this laboratory is the cellular reponse to, and repair. of damaged DNA. The goal is to understand the biochemical and structural mechanisms of the large multi-protein DNA replication and repair assemblies. Our studies focus on complexes built around replication protein A (RPA), an essential factor that protects and organizes single strand DNA as well as coordinates the assembly of protein complexes in all DNA processing events. One major project involves the recognition and processing of toxic DNA adducts via the nucleotide excision repair pathway. In all of our studies, biochemical and biophysical approaches are used to map out interaction sites between various proteins and the DNA substrate, setting the stage for detailed structural analysis using NMR, X-ray crystallography, and other structural tools. Our results are providing new insights into fundamental links between DNA replication and repair and how mutations in essential DNA processing proteins can lead to cancer and other diseases.

Recent Publications

Ball HL, Ehrhardt MR, Mordes DA, Glick GG, Chazin WJ, Cortez D. Function of a conserved checkpoint recruitment domain in ATRIP proteins. Mol Cell Biol. 2007 27:3367-77.

Weiner BE, Huang H, Dattilo BM, Nilges MJ, Fanning EE, Chazin WJ. An iron-sulfur cluster in the C-terminal domain of the p58 subunit of human DNA primase. J Biol Chem. 2007 282:33444-33451.

Chazin WJ. The impact of X-ray crystallography and NMR on intracellular calcium signal transduction by EF-hand proteins: crossing the threshold from structure to biology and medicine. Sci STKE. 2007 2007:pe27.

Dattilo BM, Fritz G, Leclerc E, Kooi CW, Heizmann CW, Chazin WJ. The extracellular region of the receptor for advanced glycation end products is composed of two independent structural units. Biochemistry. 2007 46:6957-70.

Bunick CG, Miller MR, Fuller BE, Fanning E, Chazin WJ. Biochemical and structural domain analysis of xeroderma pigmentosum complementation group C protein. Biochemistry. 2006 45:14965-79.

Jiang X, Klimovich V, Arunkumar AI, Hysinger EB, Wang Y, Ott RD, Guler GD, Weiner B, Chazin WJ, Fanning E. Structural mechanism of RPA loading on DNA during activation of a simple pre-replication complex. EMBO J. 2006 25:5516-26.

Sunahori K, Yamamura M, Yamana J, Takasugi K, Kawashima M, Yamamoto H, Chazin WJ, Nakatani Y, Yui S, Makino H. The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis. Arthritis Res Ther. 2006 8:R69.

Shah VN, Wingo TL, Weiss KL, Williams CK, Balser JR, Chazin WJ. Calcium-dependent regulation of the voltage-gated sodium channel hH1: intrinsic and extrinsic sensors use a common molecular switch. Proc Natl Acad Sci U S A. 2006 103:3592-7.

Meyn SM, Seda C, Campbell M, Weiss KL, Hu H, Pastrana-Rios B, Chazin WJ. The biochemical effect of Ser167 phosphorylation on Chlamydomonas reinhardtii centrin. Biochem Biophys Res Commun. 2006 342:342-8.

Johnson E, Chazin WJ, Rance M. Effects of calcium binding on the side-chain methyl dynamics of calbindin D9k: a 2H NMR relaxation study. J Mol Biol. 2006 357:1237-52.

Chandran V, Stollar EJ, Lindorff-Larsen K, Harper JF, Chazin WJ, Dobson CM, Luisi BF, Christodoulou J. Structure of the regulatory apparatus of a calcium-dependent protein kinase (CDPK): a novel mode of calmodulin-target recognition. J Mol Biol. 2006 357:400-10.

Vander Kooi CW, Ohi MD, Rosenberg JA, Oldham ML, Newcomer ME, Gould KL, Chazin WJ. The Prp19 U-box crystal structure suggests a common dimeric architecture for a class of oligomeric E3 ubiquitin ligases. Biochemistry. 2006 45:121-30.

Bunick CG, Chazin WJ. Two blades of the [ex]scissor. Structure. 2005 13:1740-1.

Sheehan JH, Bunick CG, Hu H, Fagan PA, Meyn SM, Chazin WJ. Structure of the N-terminal calcium sensor domain of centrin reveals the biochemical basis for domain-specific function. J Biol Chem. 2006 281:2876-81.