DNA repair, DNA replication, and UV mutagenesis

Cells that have been irradiated with ultraviolet light (UV) suffer damage t o their DNA, primarily in the form of covalent linkage between adjacent pyr imidines. Such photoproducts represent blocks to RNA and DNA polymerases an d are potentially mutagenic, Blockage of RNA polymerase II by a photoproduc t in the transcribed strand of an active gene leads to induction of the p53 protein, which induces pleiotropic responses that may include apoptotic ce ll death. Ifa cell survives, the blocked polymerase targets the nucleotide excision repair machinery to the site of the lesion, which is repaired in a n error-free manner. Repair coupled to transcription in this manner strongl y influences the mutation spectrum induced by UV, reducing the proportion o f base substitutions that arise from photoproducts on the transcribed stran d, If the damage persists when the DNA is replicated in S-phase, either bec ause the cell is unable to repair the damage or because there is insufficie nt time between the induction of damage and the onset of S-phase, To do so, the replicative DNA polymerase complex may be blocked. In this situation, lesion bypass can be accomplished using an error-free mechanism, or using a n error-prone mechanism that involves the newly described, non-processive D NA polymerase zeta encoded by the human homolog of the yeast REV3 gene.