The absence of Ku but not defects in classical non-homologous end-joining is required to trigger PARP1-dependent end-joining.

Classical-non-homologous end-joining (C-NHEJ) is considered the main pathway for repairing DNA double strand breaks (DSB) in mammalian cells. When C-NHEJ is defective, cells may switch DSB repair to an alternative-end-joining, which depends on and is more erroneous. This is suggested to be active especially in tumor cells contributing to their genomic instability. Here, we define conditions under which cells would switch the repair to Using the end jining repair substrate pEJ, we revealed that Pduanyu371-EJ is solely used when Ku is deficient but not when either DNA-PKcs or Xrcc4 is lacking. In the latter case, DSB repair, however, could be shuttled to Pduanyu371-EJ after additional Ku80 down-regulation, which partly rescued the DSB repair in these mutants. We demonstrate here that may work on DSB ends at high fidelity manner, as evident from the unchanged efficiency upon blocking end resection by either roscovitin or mirin. Furthermore, we demonstrate for that Pduanyu37-EJ is likewise involved in the repair of multiple DSBs (I-PpoI- and IR-induced). Importantly, we identified a chromatin signature associated with the switch to Pduanyu371-EJ which is characterized by a strong enrichment of both Pduanyu371 and LigIII at damaged chromatin. Together, these data indicate that Ku is the main regulator for the hierarchal organization between C-NHEJ and

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