Rejoining of Radiation-Induced DNA Double-Strand Breaks in Yeast

Abstract

Among the various lesions detected in the DNA of irradiated cells, DNA double-strand breaks (DSB) and bulky lesions (denatured regions comprising at least three unpaired bases) lead to structural disturbances which may have important biological consequences (Fig. 1). While little is known about radiation-induced bulky lesions in eukaryotes (Geigl 1987), intensive investigations on radiation-induced DNA DSB have been performed in recent years. The unicellular yeast Saccharomyces cerevisiae has contributed significantly of the understanding of the role of DSB in irradiated eukaryotic cells. This organism proved to be especially suitable to study induction and rejoining of DSB at biologically relevant radiation doses because of the small size of its chromosomal DNA molecules, allowing the detection of few DSB per cell by the neutral sucrose sedimentation technique. A haploid yeast cell contains per nucleus 16 chromosomes of varying DNA length ranging from 150 to about 2500 kb pairs. The yeast chromatin is organized in nucleosomes containing the four core histones H2A, H2B, H3, and H4, but clear evidence for the HI histone is missing (see Fangman and Zakian 1981). Unlike mammalian cells, radiation-sensitive yeast mutants exist which do not show a detectable rejoining of radiation-induced DSB. These mutants are valuable tools to investigate the biological relevance of DSB. Especially helpfull in this respect are mutants which are temperature conditional for DSB rejoining. Although yeast is an ideal organism to study the fate of DNA DSB and their role in cell killing at biologically relevant doses, cytological investigations are difficult to perform because of the small size of the yeast chromosomes.KeywordsLinear Energy TransferDose Rate ExposureOxygen Enhancement RatioRelative Biological EfficiencyRelative Molar MassThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.