SNF2H interacts with XRCC1 and is involved in repair of H2O2-induced DNA damage.
The protein XRCC1 has no inherent enzymatic activity, and is believed to function in base excision repair as a dedicated scaffold component that coordinates other DNA repair factors. Repair foci clearly represent the recruitment and accumulation of DNA repair factors at sites of damage; however, uncertainties remain regarding their organization in the context of nuclear architecture and their biological significance. Here we identified the chromatin remodeling factor SNF2H/SMARCA5 as a novel binding partner of XRCC1, with their interaction dependent on the casein kinase 2-mediated constitutive phosphorylation of XRCC1. The proficiency of repairing H2O2-induced damage was strongly impaired by SNF2H knock-down, and similar impairment was observed with knock-down of both XRCC1 and SNF2H simultaneously, suggesting their role in a common repair pathway. Most SNF2H exists in the nuclear matrix fraction, forming salt extraction-resistant foci-like structures in unchallenged nuclei. Remarkably, damage-induced formation of both PAR and XRCC1 foci depended on SNF2H, and the PAR and XRCC1 foci co-localized with the SNF2H foci. We propose a model in which a base excision repair complex containing damaged chromatin is recruited to specific locations in the nuclear matrix for repair, with this recruitment mediated by XRCC1-SNF2H interaction.
Department of Molecular Biochemistry, School of Medicine, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Shiwa, Iwate 028-3694, Japan. Electronic address: yoshikok@iwate-med.ac.jp.
Yoshiko
Y
Kubota
Department of Molecular Biochemistry, School of Medicine, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Shiwa, Iwate 028-3694, Japan.
Shinji
S
Shimizu
Department of Tumor Biology, School of Medicine, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Shiwa, Iwate 028-3694, Japan.
Shinji
S
Yasuhira
Department of Molecular Biochemistry, School of Medicine, Iwate Medical University, 2-1-1 Nishitokuta, Yahaba, Shiwa, Iwate 028-3694, Japan.
Saburo
S
Horiuchi
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D047390:Casein Kinase II / Q000235:genetics* / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D010766:Phosphorylation; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D000076105:X-ray Repair Cross Complementing Protein 1
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D004247:DNA; D006861:Hydrogen Peroxide; D047390:Casein Kinase II; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human
Chromatin structure; Foci; Nuclear matrix; Phosphorylation; SNF2H; XRCC1