Effect of double-strand break DNA sequence on the PARP-1 NHEJ pathway |
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Authors: | Audebert Marc Salles Bernard Calsou Patrick |
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Affiliation: | Institut de Pharmacologie et de Biologie Structurale, CNRS UMR5089, 205 route de Narbonne, F-31077 Toulouse, Cedex, France |
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Abstract: | Efficient repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genomic integrity. In mammalian cells, DSBs are preferentially repaired by non-homologous end-joining (NHEJ). We have previously described a new DSBs microhomology end-joining pathway depending on PARP-1 and the XRCC1/DNA ligase III complex. In this study we analysed, with recombinant proteins and protein extracts, the effect of DSB end sequences: (i) on the DSB synapsis activity; (ii) on the end-joining activity. We report that PARP-1 DSB synapsis activity is independent of the DSB sequence and could be detected with non-complementary DSBs. We demonstrate also that the efficiency of DSBs repair by PARP-1 NHEJ is strongly dependent on the presence of G:C base pairs at microhomology termini. These results highlight a new role of the PARP-1 protein on the synapsis of DSBs and could explain why the PARP-1 NHEJ pathway is strongly dependent on the DSBs microhomology sequence. |
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Keywords: | NHEJ, non-homologous end-joining HR, homologous recombination DNA-PK, DNA dependent protein kinase DSBs, DNA double-strand breaks PARP-1, poly(ADP-ribose) polymerase-1 PNK, polynucleotide kinase XL, XRCC1/DNA ligase III nt, nucleotides |
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