XRCC1 coordinates the initial and late stages of DNA abasic site repair through protein-protein interactions.
The major human AP endonuclease APE1 (HAP1, APEX, Ref1) initiates the repair of abasic sites generated either spontaneously, from attack of bases by free radicals, or during the course of the repair of damaged bases. APE1 therefore plays a central role in the base excision repair (BER) pathway. We report here that XRCC1, another essential protein involved in the maintenance of genome stability, physically interacts with APE1 and stimulates its enzymatic activities. A truncated form of APE1, lacking the first 35 amino acids, although catalytically proficient, loses the affinity for XRCC1 and is not stimulated by XRCC1. Chinese ovary cell lines mutated in XRCC1 have a diminished capacity to initiate the repair of AP sites. This defect is compensated by the expression of XRCC1. XRCC1, acting as both a scaffold and a modulator of the different activities involved in BER, would provide a physical link between the incision and sealing steps of the AP site repair process. The interaction described extends the coordinating role of XRCC1 to the initial step of the repair of DNA abasic sites.
Vidal
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AE
Département de Radiobiologie et Radiopathologie, Commissariat à l'Energie Atomique, UMR217 CNRS-CEA, BP6, F-92265 Fontenay aux Roses, France.
Boiteux
S
S
Hickson
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ID
Radicella
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JP
D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D016466:CHO Cells; D019757:Carbon-Oxygen Lyases / Q000378:metabolism*; D002384:Catalysis; D006224:Cricetinae; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair; D018076:DNA, Complementary / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000378:metabolism*; D043223:Deoxyribonuclease IV (Phage T4-Induced); D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques; D000076105:X-ray Repair Cross Complementing Protein 1
D017931:DNA Primers; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D004247:DNA; D005982:Glutathione Transferase; D043223:Deoxyribonuclease IV (Phage T4-Induced); D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase