Complex DNA damage induced by high-LET α-particles and protons triggers a specific cellular DNA damage response

Complex DNA damage (CDD), a signature of ionising radiation, contributes significantly to cell killing although the precise mechanism of recognition and processing in cellular DNA is currently unknown. By comparing cellular effects of low versus high linear energy transfer (LET) radiation, therefore varying CDD frequency, we demonstrate that histone H2B ubiquitylated on lysine 120 catalysed by MSL2 and RNF20/RNF40 complex is essential for CDD repair following high-LET α-particles and protons, and in controlling cellular radiosensitivity.

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