Carcinogenesis Laboratory, Michigan State University, East Lansing, Michigan, U.S.A.

Correspondence: Dr W. G. McGregor, Carcinogenesis Laboratory, 341 Food Safety & Tox. Bldg., Michigan State University, East Lansing, MI 48824-1302. E-mail: mcgrego3@msu.edu

Received 26 March 1999; Revised 18 June 1999; Accepted 22 June 1999.

Abstract

Cells that have been irradiated with ultraviolet light (UV) suffer damage to their DNA, primarily in the form of covalent linkage between adjacent pyrimidines. Such photoproducts represent blocks to RNA and DNA polymerases and are potentially mutagenic. Blockage of RNA polymerase II by a photoproduct in the transcribed strand of an active gene leads to induction of the p53 protein, which induces pleiotropic responses that may include apoptotic cell death. If a cell survives, the blocked polymerase targets the nucleotide excision repair machinery to the site of the lesion, which is repaired in an error-free manner. Repair coupled to transcription in this manner strongly influences the mutation spectrum induced by UV, reducing the proportion of base substitutions that arise from photoproducts on the transcribed strand. If the damage persists when the DNA is replicated in S-phase, either because the cell is unable to repair the damage or because there is insufficient 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 an error-prone mechanism that involves the newly described, nonprocessive DNA polymerase encoded by the human homolog of the yeast REV3 gene.