Involvement of Caveolin-1 in Repair of DNA Damage through Both Homologous Recombination and Non-Homologous End JoiningReport as inadecuate




Involvement of Caveolin-1 in Repair of DNA Damage through Both Homologous Recombination and Non-Homologous End Joining - Download this document for free, or read online. Document in PDF available to download.

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.

Methodology-Principal Findings

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.

Conclusion-Significance

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.



Author: Hua Zhu , Jingyin Yue, Zui Pan, Hao Wu, Yan Cheng, Huimei Lu, Xingcong Ren, Ming Yao, Zhiyuan Shen, Jin-Ming Yang

Source: http://plos.srce.hr/



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