Expanding roles of DNA repair protein RAD51 in transcription
Mentor Name: Matthew Weitzman
Fanconi anemia is a rare, multi-system disease that mostly affects children and is caused by defects in DNA repair proteins. Bone marrow failure, leukemia, and cancerous solid tumors are the most common causes of death related to Fanconi anemia. Our research is focused on a critical DNA repair factor, RAD51. While loss of RAD51 function is associated with Fanconi anemia and increased cancer risk, RAD51 upregulation in cancer also contributes to therapeutic resistance. We have identified a role for RAD51 in enhancing gene transcription.We are interested in studying how RAD51 can regulate expression of genes in healthy and cancer cells with the goal of understanding if the function of RAD51 in transcription can regulate the expression of oncogenes. To address these questions, we will generate multiple RAD51 mutant cell lines that will selectively inhibit specific functions of the protein. We will investigate the impact of these mutants on their ability to enhance or reduce gene expression. We have developed a tractable model system to study the impact of DNA repair proteins on transcription. We will use a DNA virus infection as our model system. Infection of a DNA virus initiates a sequential cascade of gene expression from the virus that can be used as a clear readout for transcription. We will determine the mechanism by which RAD51 regulates transcription and how this role is important in preventing cells from entering a diseased state.
