Mechanisms of DNA Replication and Mutagenesis in Ultraviolet-Irradiated Bacteria and Mammalian Cells

Abstract

This chapter discusses the studies on DNA replication in bacteria and mammalian cells irradiated by ultraviolet (UV) light. This topic is of interest because cellular mechanisms for replicating damaged DNA are functionally related to cellular control of UV-light-induced mutagenesis. The chapter restricts its analysis to UV damage, since a lesion in DNA that results in major biological and mutagenic effects, the pyrimidine dimer, has been identified. Other pathways for the repair of pyrimidine dimers (e.g., excision repair and photo reactivation) have been extensively reviewed and are mentioned briefly in the chapter. In particular, the chapter also discusses the effects of UV irradiation on DNA synthesis in bacteria, mammalian cells, bacteriophages, and animal viruses. Possible mechanisms for replication of damaged chromosomes are described, and the mechanisms of UV-induced mutagenesis are analyzed. Because studies performed in bacteria have frequently served as models for similar processes in mammalian cells, the bacterial studies are reviewed first. The extent to which these models apply to mammalian cell systems is discussed, and where appropriate new models are presented to explain data from mammalian cells that fail to be explained satisfactorily by the bacterial models.