DNA Replication, Recombination & Repair

Understanding mechanisms of DNA breakage and repair is fundamental to cancer research

DNA breakage can be either programmed by the cell or incidental. Programmed DNA breakage originates within the cell during normal processes and is absolutely required for meiotic crossing-over and immune system diversity. In contrast, incidental DNA breakage can result from exposure to ultraviolet radiation from the sun, chemicals present in the environment, and even the formation of reactive chemical species from reactions between oxygen and water within cells. Moreover, many cancer therapies induce irreparable DNA damage leading to cell death. Thus, understanding how cells respond to and repair DNA damage is important for understanding the causes of cancer and developing new treatments. Epigenetics and Molecular Carcinogenesis researchers are defining:

• Mechanisms of DNA double-strand break repair
• Roles of DNA polymerases in repair
• DNA damage and repair as part of normal cell function and in   carcinogenesis
• DNA damage response pathway
• Relationships between chromatin remodeling and DNA damage response and repair

When DNA damage causes cells to go awry

Department investigators are studying the protein machinery involved in several DNA repair pathways, including homologous recombination (HR) and non-homologous end-joining (NHEJ) for the repair of DNA double-strand breaks, and nucleotide excision repair for the repair of ultraviolet radiation-induced DNA damage and other strand-distorting lesions.

Faculty are also learning how programmed DNA damage and repair are involved in normal processes, such as meiosis and B-cell development, and how these processes can go awry during cancer development. Other active areas of research include investigations into how DNA polymerases synthesize new DNA at repair sites, how chromatin-modifying activities cooperate with DNA repair machinery to facilitate repair in the context of chromatin, and the mechanisms underlying the conversion of DNA damage into the mutations that cause cancer.