The genotoxic consequences of DNA damage in living organisms include short-term genetic instability and programmed cell death, as well as long-term inheritance of mutations and somatically acquired cancer. To respond to such constant genotoxic insults, living creatures from viruses to humans have evolved the capacity to remove or tolerate DNA lesions. Although the first process is generally referred to as DNA repair, the latter one has been described in the eukaryotic literature as postreplication repair, translesion synthesis, or bypass replication. Numerous lines of evidence suggest that replication of DNA lesions is often an essential triggering factor in the induction of deleterious genetic effects (1 ). First, proliferating cells are more susceptible to neoplastic transformation than nonproliferating cells after genotoxic treatment. Second, mutation rates increase dramatically during S-phase of cells pre-exposed to DNA-damaging agents. Third, DNA damage stimulates replication-dependent clastogenic phenomena in mammalian cells, such as sister-chromatid exchanges, chromosomal aberrations, and gene amplification. Fourth, several cancer-prone syndromes present constitutional abnormalities in the recovery of replication after DNA damage (seeChapter 44 ). Because of such clear evidence for the primary role played by replication of DNA lesions on processes leading to genetic instability, it is important to understand the mechanisms of lesion persistence in eukaryotic cells.
