DNA double-strand breaks: their repair and relationship to cell killing in yeast

Yeast is a suitable eukaryotic organism in which to study DNA double-strand breakage measured by the neutral sucrose gradient sedimentation technique and cell killing in the same range dose of sparsely ionizing radiations. Radiosensitive mutants (including temperature conditional ones) exist in which rejoining of double-strand breaks (dsb) is not detectable. In such mutants approximately one dsb per cell corresponds to a lethal event, suggesting that a dsb is a potentially lethal lesion. There are two modes by which dsb may confer cell lethality: firstly, an unrepaired dsb may be lethal on its own and secondly, two dsb may interact to form a lethal lesion (binary misrepair). The operationally defined cellular phenomena of potentially lethal damage (PLD) repair and sublethal damage (SLD) repair are both based on the repair of dsb. Induced dsb show a linear and unrejoined dsb a linear-quadratic relationship with dose. At low dose rate the quadratic component is abolished in accordance with the exponential survival curve observed. The dose-rate effect is based on dsb repair during irradiation; it is absent in dsb repair-deficient mutants.