Laboratory of Proteomic Biology
The Laboratory, headed by Dr. Huilin Zhou, is primarily interested in how cells respond to DNA damage. We focus on the characterization of the protein kinase cascade in the DNA damage checkpoint using budding yeast as a model organism. Importantly this kinase cascade is conserved from yeast to human, and inherited mutations to the human DNA damage checkpoint genes are often linked to inherited genome instability syndromes like cancers. We are particularly interested in understanding the mechanism of the regulations and functions of the kinase cascade using several complementary approaches. First, we are working towards a biochemical reconstitution of the phosphorylation events in this kinase cascade in vitro. Combined with mass spectrometric analysis of the in vivo phosphorylation of these kinases, we are dissecting the various pathways involved in DNA damage checkpoint activation. Second, by taking advantage of the power of yeast genetics, we are investigating how various pathways involved in DNA damage checkpoint activation are regulated by various DNA damage checkpoint genes, and how each pathway contributes to distinct cellular responses including sensitivities to various types of DNA damage, telomere maintenance, suppression of genome instabilities and others. Third, we have developed several proteomics technologies, which allow the identification of novel protein-protein interactions associated with those that function in the DNA damage checkpoint, and a quantitative analysis of the in vivo phosphorylation of virtually any yeast protein of interest.
