DNA Damage, Repair and Mutagenesis

Understanding DNA Damage is Crucial for the Study of Cancer

DNA is subjected to damage from many sources, including inescapable chemical reactions with oxygen and water. Other sources include ultraviolet radiation from the sun and chemicals that are present in the environment. If DNA is not properly repaired, cells will accumulate mutations, which can drive cancer development. Moreover, many cancer therapies cause DNA damage as the mechanism of action to kill cancer cells. Thus, studying how cells respond to and repair DNA damage is important for understanding both the causes of cancer and its treatment.

When DNA Damage Goes Awry

Investigators in the department are studying the protein machinery involved in several DNA repair pathways, including homologous recombination and non-homologous end-joining 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. Our faculty are also studying 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 chromatin-modifying activities cooperate with the DNA repair machinery to facilitate repair in the context of chromatin and the mechanisms involved in converting DNA damage to the mutations that cause cancer.

Elucidating the DNA Damage Response Signaling Pathways

Studies in the department are also focused on DNA damage response signaling pathways that induce cell cycle checkpoints and alter transcriptional programs. DNA damage response signaling is critical for maintaining genome integrity and is often inactivated in cancers (e.g., p53 mutations). These responses also include mechanisms that allow cells to tolerate and survive DNA damage. Research in these related areas employs a broad range of approaches ranging from fundamental biochemical studies of purified proteins to cell biology to genetically engineered mouse models with impaired DNA damage response and repair pathways.