Distinct spatiotemporal patterns and PARP dependence of XRCC1 recruitment to single-strand break and base excision repair.
Single-strand break repair (SSBR) and base excision repair (BER) of modified bases and abasic sites share several players. Among them is XRCC1, an essential scaffold protein with no enzymatic activity, required for the coordination of both pathways. XRCC1 is recruited to SSBR by PARP-1, responsible for the initial recognition of the break. The recruitment of XRCC1 to BER is still poorly understood. Here we show by using both local and global induction of oxidative DNA base damage that XRCC1 participation in BER complexes can be distinguished from that in SSBR by several criteria. We show first that XRCC1 recruitment to BER is independent of PARP. Second, unlike SSBR complexes that are assembled within minutes after global damage induction, XRCC1 is detected later in BER patches, with kinetics consistent with the repair of oxidized bases. Third, while XRCC1-containing foci associated with SSBR are formed both in eu- and heterochromatin domains, BER complexes are assembled in patches that are essentially excluded from heterochromatin and where the oxidized bases are detected.
CEA, Institute of Cellular and Molecular Radiobiology, F-96265 Fontenay aux Roses, France. anna.campalans@cea.fr
Anna
A
Campalans
Thierry
T
Kortulewski
Rachel
R
Amouroux
Hervé
H
Menoni
Wim
W
Vermeulen
J Pablo
JP
Radicella
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D022041:Euchromatin / Q000235:genetics / Q000378:metabolism; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D010084:Oxidation-Reduction; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D059010:Single-Cell Analysis; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D022041:Euchromatin; D006570:Heterochromatin; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C000619352:Xrcc1 protein, mouse; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human