The high toxicity of DSB-clusters modelling high-LET-DNA damage derives from inhibition of c-NHEJ and promotion of alt-EJ and SSA despite increases in HR.

An additional reason for this choice is that recent work demonstrates unexpected but highly significant mechanistic shifts in DDR and DSB-repair, depending not only upon the phase of the cell-cycle cells are irradiated, but also the phase of the cell-cycle responses are analyzed ( Mladenov et al., 2019a ; Mladenov et al., 2019b ; Mladenov et al., 2020 ).

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