Damage-resistant DNA synthesis in Eukaryotes

Abstract

The molecular basis of sensitivity of ionizing radiation and other damaging agents is not clearly defined in eukaryotes. While a large number of mutants have been described only a few have been demonstrated to have a defect in the repair of damage to DNA. An interesting characteristic of a sub-group of these mutants, in different species extending throughout the phylogenetic scale, is the presence of damage-resistant DNA synthesis. This phenomenon is observed in cells from individuals with the genetic disorder ataxia telangiectasia, in HeLa cells treated with fluorodeoxyuridine prior to UV irradiation, in mutants of the fungus Neurospora crassa, the slime mould Dictyostelium discoideum, the fruit fly Drosophila melanogaster and possibly in the “wasted” mouse mutant. In the case of ataxia telangiectasia sensitivity is only observed to ionizing radiation or radiomimetic chemicals whereas sensitivity to a wider spectrum of mutagens is reported for the lower eukaryotic mutants. In all cases a reduced inhibition of DNA synthesis is obtained after exposure to an agent to which the cell type is hypersensitive. It is unclear how damage-resistant DNA synthesis contributes to increased sensitivity in these cells, but is unlikely to be the major mechanism predisposing to radiation-induced cell death. The description of a derivative of an ataxia telangiectasia cell line with normal sensitivity to radiation but still maintaining resistant DNA synthesis partially uncouples radioresistant DNA synthesis and radiosensitivity. This paper is designed to review the phenomenon of damage-resistant DNA synthesis in a number of mutants.