Potentially lethal damage, sublethal damage and DNA double strand breaks

In yeast mutants deficient in the repair of DNA double strand breaks (DSBs) one DSB per cell corresponds to one lethal event. This suggests that an unrepaired DSB may lead to cell death and, by definition, a DSB may represent a potentially lethal lesion. Support for this comes from the observation that liquid holding recovery of colony forming ability is due to the repair of DSBs. The shape of survival curves is determined by the extent of DSB repair allowed to occur in cells after irradiation. DSB repair affects both the shoulder width and the slope of survival curves. Repair of sublethal damage, as deduced from split dose experiments, is due to the repair of DSB. From these results it is concluded that DSBs may lead to cell killing by two mechanisms: firstly, a DSB is lethal on its own and secondly, at least two DSBs may interact to form a lethal lesion. Thus, both the radiobiological phenomena ''repair of potentially lethal damage'' and ''repair of sublethal damage'' can be interpreted in terms of the same molecular lesion, the DNA double strand break. (author)