Genomic integrity maintenance is a fundamental function to sustain life due to the fact that DNA alterations such as mutations, chromosomal rearrangements, and deletions are causative factors of disease, tumorigenesis, and cell death. Cells encounter a large number of DNA lesions on a daily basis, jeopardizing the integrity of the genome, with DNA double-strand breaks (DSBs) being the most significant. The deleterious nature of DSBs is underscored by the fact that a single unrepaired DSB can cause cell death and misrepaired DSBs can result in chromosomal aberrations such as translocations and large-scale deletions. Chromosomal aberrations can result in genomic instability, a hallmark of cancer development. The cellular response to DSBs is extensive and includes recognition of the DNA lesion, signal transduction responses including modulation of the cell cycle, and, finally, repair of the DSB.
The goal of the Davis lab is to uncover the mechanisms that modulate the cellular response to DSBs. We are motivated by the fact that a more complete understanding of these mechanisms will provide insight into how cells protect their genome and how dysregulation of these mechanisms can drive cancer etiology and how they could potentially be exploited to lead to the development of more effective cancer therapies.