Mechanisms of Mutagenesis and Genome Alterations

The 2016 Mutagenesis GRC will focus on conserved molecular mechanisms of mutagenesis, and how these mechanisms contribute to human diseases such as aging and cancer. Mutations are changes in DNA sequence, which range from single base pair alterations to complex genome rearrangements, which are hallmarks of cancer cells. Metabolic and environmental stresses are major contributors to mutagenesis, and leads to the increased risk of disease, including accelerated aging and age-related diseases such as cancer and neurodegeneration. Moreover, germ line mutations confer inherited diseases, including a wide range of rare diseases and childhood disorders. Conversely, mutagenesis also plays a positive biological role in driving diversity and promoting speciation. Mutagenic mechanisms are also essential for the development of the human immune system, in which the evolution of high-affinity antibodies following exposure to a new antigen depends on the targeted mutation of immunoglobulin genes. The Mutagenesis GRC uniquely addresses the mechanisms and outcomes of mutagenesis in diverse experimental systems. Recent findings by our selected speakers have revealed important new insights into the mechanisms of spontaneous and targeted mutagenesis and the impact on human disease. The conference will highlight new work encompassing a broad range of approaches, from mechanistic studies of mutagenesis, to the recent revolution in whole-genome analysis, to new therapeutic approaches.