The relevance of the nuclear division cycle to radiosensitivity in yeast

Summary

To investigate whether the nuclear division cycle could be related to cycle-specific changes in repair of ionizing radiation damage, we have determined the survival curves after γ-irradiation of samples taken frequently from synchronously dividing cultures of Saccharomyces cerevisiae cells. Survival was low in G1 and increased during S, reaching a maximum around the end of the S phase, which was maintained in G2. The shape of the survival curves for samples taken from later stages revealed a rapid cycle-specific drop in the radioresistance of individual cells. A simple model was formulated on the assumption that survival is greatly enhanced by the action of an enzymatic repair mechanism which requires duplicated but unsegregated DNA as a substrate. By taking into account the measurable age heterogeneity of samples taken from the synchronous cultures, this model was shown to fit the survival data closely. For an individual cell, the increasing survival during the S phase is thus attributable to a rising fraction of duplicated genome, whereas the rapid decrease in radioresistance at a later stage in the cell cycle may be interpreted as due to the final physical separation of sister chromatids. The start of the latter event was timed to the stage in mitosis when the nucleus begins to move towards the neck of the bud. The data are consistent with the hypothesis that the high radioresistance of cells in late S and G2 is due to the repair of double-stranded DNA breaks by a process involving recombination between sister chromatids.