Genomic DNA is damaged tens of thousands of times per day in every cell. This damage occurs as a consequence of environmental insults and because electrophilic genotoxins are generated endogenously as by-products of metabolism. Maintaining the integrity of the genetic code is essential for the viability and proper functioning of cells. The fact that DNA repair mechanisms are amongst the most evolutionarily conserved of pathways also testifies to the importance of genome maintenance. Genetic diseases in which DNA repair mechanisms are affected reveal the biological consequences of DNA damage. We identified a single gene (XPF) that when mutated in humans can lead to a profound risk of cancer or rapidly accelerated aging. We modeled this in the mouse to create an experimental system in which study the relationship between DNA damage, cancer and aging.

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