title: Involvement of Caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining.
abstract: BACKGROUND
  Caveolin-1 (Cav-1), the major component of caveolae, is a 21-24 kDa integral membrane protein that interacts with a number of signaling molecules. By acting as a scaffolding protein, Cav-1 plays crucial roles in the regulation of various physiologic and patho-physiologic processes including oncogenic transformation and tumorigenesis, and tumor invasion and metastasis.
  
  
  RESULTS
  In the present study we sought to explore the role of Cav-1 in response to DNA damage and the mechanism involved. We found that the level of Cav-1 was up-regulated rapidly in cells treated with ionizing radiation. The up-regulation of Cav-1 following DNA damage occurred only in cells expressing endogenous Cav-1, and was associated with the activation of DNA damage response pathways. Furthermore, we demonstrated that the expression of Cav-1 protected cells against DNA damage through modulating the activities of both the homologous recombination (HR) and non-homologous end joining (NHEJ) repair systems, as evidenced by the inhibitory effects of the Cav-1-targeted siRNA on cell survival, HR frequency, phosphorylation of DNA-dependent protein kinase (DNA-PK), and nuclear translocation of epidermal growth factor receptor (EGFR) following DNA damage, and by the stimulatory effect of the forced expression of Cav-1 on NHEJ frequency.
  
  
  CONCLUSIONS
  Our results indicate that Cav-1 may play a critical role in sensing genotoxic stress and in orchestrating the response of cells to DNA damage through regulating the important molecules involved in maintaining genomic integrity.
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey, United States of America. zhuhu2@umdnj.edu
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.forename: Jingyin
authors.initials: J
authors.lastname: Yue
authors.forename: Zui
authors.initials: Z
authors.lastname: Pan
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Huimei
authors.initials: H
authors.lastname: Lu
authors.forename: Xingcong
authors.initials: X
authors.lastname: Ren
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Shen
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Yang
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D020868:Gene Silencing; D006801:Humans; D011995:Recombination, Genetic; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D051242:Caveolin 1; D004247:DNA