Involvement of caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining

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

Research output: Contribution to journalArticle

24 Citations (Scopus)

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. Methodology/Principal Findings: In the present study we sought to explore the role of Cav-1 in response toDNAdamage 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.

Original languageEnglish (US)
Article numbere12055
JournalPloS one
Volume5
Issue number8
DOIs
StatePublished - Oct 15 2010

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Caveolin 1
Homologous Recombination
homologous recombination
Joining
DNA damage
DNA Damage
Repair
DNA
scaffolding proteins
cells
small interfering RNA
ionizing radiation
membrane proteins
metastasis
protein kinases
carcinogenesis
cell viability
phosphorylation
Cells
DNA-Activated Protein Kinase

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Zhu, Hua ; Yue, Jingyin ; Pan, Zui ; Wu, Hao ; Cheng, Yan ; Lu, Huimei ; Ren, Xingcong ; Yao, Ming ; Shen, Zhiyuan ; Yang, Jin-Ming. / Involvement of caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining. In: PloS one. 2010 ; Vol. 5, No. 8.
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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. Methodology/Principal Findings: In the present study we sought to explore the role of Cav-1 in response toDNAdamage 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.",
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Zhu, H, Yue, J, Pan, Z, Wu, H, Cheng, Y, Lu, H, Ren, X, Yao, M, Shen, Z & Yang, J-M 2010, 'Involvement of caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining', PloS one, vol. 5, no. 8, e12055. https://doi.org/10.1371/journal.pone.0012055

Involvement of caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining. / Zhu, Hua; Yue, Jingyin; Pan, Zui; Wu, Hao; Cheng, Yan; Lu, Huimei; Ren, Xingcong; Yao, Ming; Shen, Zhiyuan; Yang, Jin-Ming.

In: PloS one, Vol. 5, No. 8, e12055, 15.10.2010.

Research output: Contribution to journalArticle

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T1 - Involvement of caveolin-1 in repair of DNA damage through both homologous recombination and non-homologous end joining

AU - Zhu, Hua

AU - Yue, Jingyin

AU - Pan, Zui

AU - Wu, Hao

AU - Cheng, Yan

AU - Lu, Huimei

AU - Ren, Xingcong

AU - Yao, Ming

AU - Shen, Zhiyuan

AU - Yang, Jin-Ming

PY - 2010/10/15

Y1 - 2010/10/15

N2 - 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 toDNAdamage 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.

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