This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
This project seeks to understand the role of the DNA damage response protein UmuD in managing DNA polymerases via its direct interactions with DNA polymerases and their accessory factors. DNA is under constant attack from harmful agents from both within and outside the cell. Such agents can cause damage to the DNA and can result in mutagenesis. Bacterial cells possess a global response that is induced when cells experience stress, including damage to their DNA. Among the genes whose expression is elevated as part of the response are specialized DNA polymerases that can copy over damaged DNA, and their manager protein UmuD. In addition to its interactions with DNA polymerases, UmuD also interacts with the beta processivity clamp, which is a protein that dramatically increases the efficiency of DNA replication. UmuD also seems to interact with an alternate form of the beta processivity clamp. This research project will probe the cellular consequences of these protein-protein interactions in the response to DNA damage. Protein-protein interactions and the composition of complexes will be probed with complementary biophysical techniques. Moreover, because the mutagenic activity of specialized DNA polymerases is thought to contribute to mutagenesis, this research will provide insights into the general process of mutagenesis and natural selection.
The broader impacts of this project include extensive opportunities for integration of students into the research laboratory. A new course in Chemical Biology has been developed, which includes research-related laboratory exercises related to ongoing research in the Department. A summer program will provide research experiences for undergraduates from diverse backgrounds. The summer research program will also provide structured professional development opportunities for students such as building communication skills in science and the responsible conduct of research. The interdisciplinary approach of the project will lead to insights into the fundamental nature of the DNA damage response, mutagenesis and bacterial evolution. The cross-cutting nature of the work also provides an excellent training opportunity for students.
