Beclin 1 and UVRAG confer protection from radiation-induced DNA damage and maintain centrosome stability in colorectal cancer cells

Jae Myung Park, David Tougeron, Shengbing Huang, Koichi Okamoto, Frank A Sinicrope

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Beclin 1 interacts with UV-irradiation-resistance-associated gene (UVRAG) to form core complexes that induce autophagy. While cells with defective autophagy are prone to genomic instability that contributes to tumorigenesis, it is unknown whether Beclin1 or UVRAG can regulate the DNA damage/repair response to cancer treatment in established tumor cells. We found that siRNA knockdown of Beclin 1 or UVRAG can increase radiation-induced DNA double strand breaks (DSBs), shown by pATM and γH2Ax, and promote colorectal cancer cell death. Furthermore, knockdown of Beclin 1, UVRAG or ATG5 increased the percentage of irradiated cells with nuclear foci expressing 53BP1, a marker of nonhomologous end joining but not RAD51 (homologous recombination), compared to control siRNA. Beclin 1 siRNA was shown to attenuate UVRAG expression. Cells with a UVRAG deletion mutant defective in Beclin 1 binding showed increased radiation-induced DSBs and cell death compared to cells with ectopic wild-type UVRAG. Knockdown of Beclin 1 or UVRAG, but not ATG5, resulted in a significant increase in centrosome number (γ-tubulin staining) in irradiated cells compared to control siRNA. Taken together, these data indicate that Beclin 1 and UVRAG confer protection against radiation-induced DNA DSBs and may maintain centrosome stability in established tumor cells.

Original languageEnglish (US)
Article numbere100819
JournalPLoS One
Volume9
Issue number6
DOIs
StatePublished - Jun 23 2014

Fingerprint

centrosomes
radiation resistance
Centrosome
Radiation Protection
colorectal neoplasms
DNA damage
DNA Damage
Colorectal Neoplasms
Genes
Cells
Irradiation
Radiation
DNA
Small Interfering RNA
small interfering RNA
genes
Double-Stranded DNA Breaks
Autophagy
autophagy
Cell death

ASJC Scopus subject areas

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

Cite this

Beclin 1 and UVRAG confer protection from radiation-induced DNA damage and maintain centrosome stability in colorectal cancer cells. / Park, Jae Myung; Tougeron, David; Huang, Shengbing; Okamoto, Koichi; Sinicrope, Frank A.

In: PLoS One, Vol. 9, No. 6, e100819, 23.06.2014.

Research output: Contribution to journalArticle

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