Principal Investigator Leona Samson
Project Website http://samsonlab.mit.edu/geneenvironment.htm
When cells are exposed to DNA damaging agents a signal is generated such that the transcription of various genes is altered. We have used Affymetrix oligonucleotide DNA chip analysis to monitor the transcriptional response of the entire S. cerevisiae genome (i.e., all 6,200 genes) in response to a number of different alkylating agents. To our surprise, we have identified hundreds of responsive genes and have uncovered a hitherto unknown response that links ubiquitin-mediated protein degradation and DNA repair. We are currently exploring the biological roles that the large number of responsive genes plays in protecting cells against alkylation toxicity. Signals can also be generated, in cells exposed to alkylating agents, which trigger cell cycle checkpoint arrest or apoptosis. We are also dissecting the molecular mechanisms by which alkylating agents signal these very important downstream events.