Presentation:
DNA repair enzymes: structure, chemistry and disease

Bio

I grew up in Shanghai, China and entered Fudan University to study Biochemistry in 1980. In 1983 I went to US to finish my last college year at the State University of New York at Stony Brook. In 1985, I chose the Columbia University to pursue graduate studies in the Department of Biochemistry and Biophysics. Under the tutelage of Dr. Wayne Hendrickson, I determined the first protein structure (RNase H1) using the seleno-methionine substitution and multiwavelength anomalous scattering (MAD) method. After obtaining the doctoral degree in 1991, I went to the laboratory of Tom Steitz at Yale University to be a postdoctoral fellow. There I was introduced to the protein-DNA world and determined the crystal structure of a site-specific recombinase (gd-resolvase) complexed with a 34 bp substrate DNA. I started my own research group at NIH in 1995.

Taking a multifaceted approach of X-ray, electron microscopy, mutagenesis, enzymology, protein and nucleic acid chemistry, my research group has made a number of seminal discoveries in DNA mismatch repair, translesion DNA synthesis, and V(D)J recombination. We discovered the ATPase activity in MutL and the proofreading function of the MutS ATPase. We have also uncovered molecular mechanisms of translesion DNA synthesis, mechano-chemical coupling at the atomic resolution and Holliday junction resolution. Most recently, to understand how RAG1 and RAG2 proteins initiate the V(D)J recombination essential for our adaptive immune system development, we have made a stable RAG-DNA complex. After characterization by electron and atomic force microscopy, we are pursuing the atomic resolution structure by X-ray crystallography.

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