Effect of double-strand break DNA sequence on the PARP-1 NHEJ pathway

• Published in: Biochemical and biophysical research communications Vol. 369; no. 3; pp. 982 - 988
• Main Authors: Audebert, Marc, Salles, Bernard, Calsou, Patrick
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.05.2008
• Subjects: Base Composition; Base Sequence; DNA - chemistry; DNA - metabolism; DNA ligase III; DNA Repair; HeLa Cells; Humans; Microhomology; NHEJ; PARP-1; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases - chemistry; Poly(ADP-ribose) Polymerases - metabolism; Recombination, Genetic; XRCC1; DSBs; XL; nt; Microhomology; XRCC1; HR; NHEJ; PNK; DNA–PK; PARP-1; DNA repair; DNA ligase III
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.11.132

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.