Ornithine decarboxylase antizyme upregulates DNA-dependent protein kinase and enhances the nonhomologous end-joining repair of DNA double-strand breaks in human oral cancer cells

Takanori Tsuji, Miki Katsurano, Soichiro Ibaragi, Kaori Shima, Akira Sasaki, Guo Fu Hu

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Ornithine decarboxylase (ODC) antizyme targets ODC for ubiquitin- independent proteosome degradation, thereby inhibiting polyamine synthesis. It has been shown to regulate DNA methylation and has tumor suppressor activity. Increasing evidence suggested that antizyme may also have ODC-independent functions. Here, we report that antizyme plays a role in DNA double-strand break repairs. A zinc-inducible human antizyme gene expression vector was transfected into UM1 human oral squamous cancer cells that do not express endogenous antizyme. The resultant upregulated genes were screened by cDNA arrays and confirmed by quantitative real-time polymerase chain reaction. DNA-dependent protein kinase including its catalytic subunit DNA-PKcs and regulatory subunit Ku70, two key proteins of the DNA damage repair machinery, was significantly upregulated after ectopic expression of antizyme. Consistently, we found that UM1 cells are sensitive to γ irradiation and deficient in DNA damage repairs, as shown by radio-sensitivity and Comet assays. Ectopic expression of antizyme increased radio-resistance of UM1 cells and restored their capacity of DNA damage repairs to the level of UM2 cells that have an identical genetic background but express endogenous antizyme. Plasmid end-joining assays confirmed that antizyme enhances the ability of UM1 cells to repair DNA double-strand breaks by the nonhomologous end-joining pathway.

Original languageEnglish
Pages (from-to)8920-8932
Number of pages13
JournalBiochemistry
Volume46
Issue number31
DOIs
Publication statusPublished - Aug 7 2007

ASJC Scopus subject areas

  • Biochemistry

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