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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The absence of Ku but not defects in classical non-homologous end-joining is required to trigger PARP1-dependent end-joining
DNA Repair, Volume 12, No. 12, Year 2013
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Description
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 PARP1 and is more erroneous. This PARP1-EJ 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 PARP1-EJ. Using the end jining repair substrate pEJ, we revealed that PARP1-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 PARP1-EJ after additional Ku80 down-regulation, which partly rescued the DSB repair in these mutants. We demonstrate here that PARP-EJ 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 PARP-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 PARP1-EJ which is characterized by a strong enrichment of both PARP1 and LigIII at damaged chromatin. Together, these data indicate that Ku is the main regulator for the hierarchal organization between C-NHEJ and PARP1-EJ. © 2013 Elsevier B.V.
Authors & Co-Authors
Mansour, Wael Yassin
Germany, Hamburg
Medical Center
Egypt, Giza
Cairo University
Borgmann, Kerstin
Germany, Hamburg
Medical Center
Petersen, Cordula
Germany, Hamburg
Universitätsklinikum Hamburg-eppendorf
Dikomey, Ekkehard
Germany, Hamburg
Medical Center
Dahm-Daphi, Jochen
Germany, Hamburg
Medical Center
Statistics
Citations: 42
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1016/j.dnarep.2013.10.005
ISSN:
15687864
e-ISSN:
15687856
Research Areas
Cancer
Genetics And Genomics