Background | Projects

Background

Alkylating agents represent environmental contaminants that can promote carcinogenesis via DNA damage and a major class of chemotherapeutics used to kill cancer cells. We study cellular responses to alkylation damage, with research projects centered on the analysis of DNA repair and signaling networks utilized after exposure or treatment with an alkylating agent. In their simplest form, alkylating agents transfer a methyl group to nucleophilic centers found in DNA, which can induce cell death and mutation. Fortunately, most cells can repair DNA alkylation damage using DNA repair enzymes that recognize, remove, and replace damaged DNA. We are interested in understanding how the activity of DNA repair enzymes are coordinated in the cell after DNA damage, with the goals of identifying key regulatory strategies and control points for DNA repair enzymes. To do this, we uses (1) high throughput systems based approaches and computer modeling to gain insight into genetic requirements and signaling programs used to respond to DNA alkylation damage; (2) molecular interaction technologies, along with kinetic and thermodynamic analysis, to construct and evaluate input and output modulators of DNA repair activities and (3) genetic and biochemical methods to study a novel damage-induced regulatory mechanism that modulates the translation of DNA repair proteins.

Figure 1. Alkylating agents can damage cellular DNA, RNA and proteins. Failure to remove the damaging effects of alkylating agents
can lead to cell death and mutation, precursors to cancer, ageing and other diseases