DNA-REPAIR FUNCTIONS IN HETEROLOGOUS CELLS

Our genetic information is constantly challenged by exposure to endoge nous and exogenous DNA-damaging agents, by DNA polymerase errors, and thereby inherent instability of the DNA molecule itself. The integrity of our genetic information is maintained by numerous DNA repair pathw ays, and the importance of these pathways is underscored by their rema rkable structural and functional conservation across the evolutionary spectrum. Because of the highly conserved nature of DNA repair, the en zymes involved in this crucial function are often able to function in heterologous cells; as an example, the E. call Ada DNA repair methyltr ansferase functions efficiently in yeast, in cultured rodent and human cells, in transgenic mice, and in ex viva-modified mouse bone marrow cells. The heterologous expression of DNA repair functions has not onl y been used as a powerful cloning strategy, but also for the explorati on of the biological and biochemical features of numerous enzymes invo lved in DNA repair pathways. In this review we highlight examples wher e the expression of DNA repair enzymes in heterologous cells was used to address fundamental questions about DNA repair processes in many di fferent organisms.