We seek to understand how cellular DNA repair works by investigating the structures and dynamics of protein-DNA complexes involved in DNA damage sensing and repair using X-ray crystallography and various biochemical/biophysical techniques.

The constituent of our genome, DNA is continuously under attacks from the surrounding, which give rise to a plethora of DNA damage. If the lesions are left unrepaired, they can result in mutations in critical genes, which may cause uncontrolled cell growth leading to cancer. Luckily, cells are equipped with intricate networks of proteins that cure the lesions in a timely manner. In particular, the nucleotide excision repair (NER) pathway repairs a broad range of DNA lesions generated by ultraviolet light and various chemicals from the environmental pollutants, and defects in this pathway can cause predisposition to cancer (as exemplified in xeroderma pigmentosum) as well as neurological and developmental abnormalities. NER proceeds in a stepwise manner by sequentially recruiting multiple factors onto the damage site. The xeroderma pigmentosum C (XPC) protein plays a key role in initiating NER in the global genome by recognizing diverse DNA damage and recruiting the downstream factor, transcription factor TFIIH complex. We are currently focusing on understanding the detailed mechanism of the damage recognition and subsequent repair steps in NER involving XPC (Rad4 in yeast). Outcome of our research provides an atomic-level understanding of the repair mechanisms and sheds lights on the underlying cause of the related diseases.