Role of multifunctional transcription factor TFII-I and putative tumour suppressor DBC1 in cell cycle and DNA double strand damage repair

M. Tanikawa, O. Wada-Hiraike, N. Yoshizawa-Sugata, A. Shirane, M. Hirano, H. Hiraike, Y. Miyamoto, K. Sone, Y. Ikeda, T. Kashiyama, K. Oda, K. Kawana, Y. Katakura, T. Yano, H. Masai, A. L. Roy, Y. Osuga, T. Fujii

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Abstract

Background:In multicellular organisms, precise control of cell cycle and the maintenance of genomic stability are crucial to prevent chromosomal alterations. The accurate function of the DNA damage pathway is maintained by DNA repair mechanisms including homologous recombination (HR). Herein, we show that both TFII-I and DBC1 mediate cellular mechanisms of cell-cycle regulation and DNA double strand damage repair.Methods:Regulation of cell cycle by TFII-I and DBC1 was investigated using Trypan blue dye exclusion test, luciferase assay, and flow cytometry analysis. We also analysed the role of TFII-I and DBC1 in DNA double strand damage repair after irradiation by immunofluorescence study, clonogenicity assay, and HR assay.Results:Flow cytometry analysis revealed a novel function that siRNA-mediated knockdown of endogenous DBC1 resulted in G2/M phase arrest. We also have shown that both endogenous TFII-I and DBC1 activate DNA repair mechanisms after irradiation because irradiation-induced foci formation of TFII-I-γH2AX was observed, and the depletion of endogenous TFII-I or DBC1 resulted in the inhibition of normal HR efficiency.Conclusion:These results reveal novel mechanisms by which TFII-I and DBC1 can modulate cellular fate by affecting cell-cycle control as well as HR pathway.

Original languageEnglish
Pages (from-to)3042-3048
Number of pages7
JournalBritish journal of cancer
Volume109
Issue number12
DOIs
Publication statusPublished - Dec 10 2013

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All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Tanikawa, M., Wada-Hiraike, O., Yoshizawa-Sugata, N., Shirane, A., Hirano, M., Hiraike, H., ... Fujii, T. (2013). Role of multifunctional transcription factor TFII-I and putative tumour suppressor DBC1 in cell cycle and DNA double strand damage repair. British journal of cancer, 109(12), 3042-3048. https://doi.org/10.1038/bjc.2013.532