Involvement of Caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining.
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.
Zhu
Hua
H
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
Yue
Jingyin
J
Pan
Zui
Z
Wu
Hao
H
Cheng
Yan
Y
Lu
Huimei
H
Ren
Xingcong
X
Yao
Ming
M
Shen
Zhiyuan
Z
Yang
Jin-Ming
JM
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
D051242:Caveolin 1; D004247:DNA