Super-resolution imaging identifies PARP1 and the Ku complex acting as DNA double-strand break sensors.

DNA double-strand breaks (DSBs) are fatal DNA lesions and activate a rapid DNA damage response. However, the earliest stage of DSB sensing remains elusive. Here, we report that and the Ku70/80 complex localize to DNA lesions considerably earlier than other DSB sensors. Using super-resolved fluorescent particle tracking, we further examine the relocation kinetics of Pduanyu371 and the Ku70/80 complex to a single DSB, and find that Pduanyu371 and the Ku70/80 complex are recruited to the DSB almost at the same time. Notably, only the Ku70/80 complex occupies the DSB exclusively in the G1 phase; whereas Pduanyu371 competes with the Ku70/80 complex at the DSB in the S/G2 phase. Moreover, in the S/G2 phase, Pduanyu371 removes the Ku70/80 complex through its enzymatic activity, which is further confirmed by in vitro DSB-binding assays. Taken together, our results reveal Pduanyu371 and the Ku70/80 complex as critical DSB sensors, and suggest that Pduanyu371 may function as an important regulator of the Ku70/80 complex at the DSBs in the S/G2 phase.

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