Maintaining genome integrity.

Introduction Genomes have always been vulnerable to damage from intraand extracellular sources such as oxidative species generated by cell metabolism, spontaneous base loss or modification, radiation and chemicals (Friedberg et al, 2005a). As a result, mechanisms to cope with DNA damage developed early in evolution and have been conserved. Organisms need some genome stability, but must allow mutational changes to drive adaptation and evolution. How this is achieved has been the subject of much interest primarily because, in humans, defects in maintaining genome stability are associated with susceptibility to cancer, abnormal immune responses and genetic disease (Friedberg et al, 2005a). This conference on Responses to DNA Damage conveyed an understanding of the complexity of repair and included reports on the intimate details of how enzymes recognize and remove certain DNA lesions. Fig 1 summarizes the DNA repair mechanisms covered in this report; it shows those that remove DNA damage and those that allow cells to tolerate damage.