Tue, Dec. 8, 2015, 3:15pm - 4:15pm
Frick Chemistry Laboratory, Taylor Auditorium
Host: Thomas Muir
Chemical Approaches to Illuminate Cellular Mechanisms Ensuring Genome Stability
The maintenance of genome stability is a major challenge faced by cells and errors in this process can lead to developmental defects and diseases such as cancer. In this seminar, I will describe the development and application of chemical tools to investigate fundamental molecular mechanisms ensuring genome stability. Using a chemical proteomics approach, we profiled, in native proteomes, direct binders of the phosphorylated histone variant, gH2AX, a central mediator of DNA double-strand break repair. These studies led to the identification of proteins that ‘read’ gH2AX, including the DNA repair protein, 53BP1, whose localization at chromosomal DNA breaks was shown to involve direct recognition of this phospho-‘mark’. I will also highlight progress towards profiling histone-mediated interactions in living cells involved in accurate chromosome segregation. This work shows how recognition of specific chemical epitopes within chromatin contributes to essential mechanisms that maintain genome stability, and demonstrates the utility of chemical approaches for the discovery and characterization of macromolecular interactions occurring in the cellular context.