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Base excision repair (BER), a major pathway for the removal of simple lesions in DNA, requires the co-ordinated action of several repair and ancillary proteins, the impairment of which can lead to genetic instability. We here address the role of poly(ADP-ribose) polymerase-1 (PARP-1) in BER. Using an in vitro cross-linking assay, we reveal that PARP-1 is always involved in repair of a uracil-containing oligonucleotide and that it binds to the damaged DNA during the early stages of repair. Inhibition of PARP-1 poly(ADP-ribosyl)ation by 3-aminobenzamide blocks dissociation of PARP-1 from damaged DNA and prevents further repair. We find that excessive poly(ADP-ribosyl)ation occurs when repair intermediates containing single-strand breaks are in excess of the repair capacity of the cell extract, suggesting that repeated binding of PARP-1 to the nicked DNA occurs. We also find increased sensitivity of repair intermediates to nuclease cleavage in PARP-deficient mouse fibroblasts and after depletion of PARP-1 from HeLa whole cell extracts. Our data support the model in which PARP-1 binding to DNA single-strand breaks or repair intermediates plays a protective role when repair is limited.

Original publication




Journal article



Publication Date





2012 - 2021


Animals, Base Sequence, Cell Extracts, Cell Line, Cross-Linking Reagents, DNA, DNA Damage, DNA Polymerase beta, DNA Repair, DNA-Binding Proteins, Enzyme Inhibitors, HeLa Cells, Humans, Mice, Models, Biological, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerase Inhibitors, Poly(ADP-ribose) Polymerases, Protein Binding, X-ray Repair Cross Complementing Protein 1