TY - JOUR
T1 - Role of multifunctional transcription factor TFII-I and putative tumour suppressor DBC1 in cell cycle and DNA double strand damage repair
AU - Tanikawa, M.
AU - Wada-Hiraike, O.
AU - Yoshizawa-Sugata, N.
AU - Shirane, A.
AU - Hirano, M.
AU - Hiraike, H.
AU - Miyamoto, Y.
AU - Sone, K.
AU - Ikeda, Y.
AU - Kashiyama, T.
AU - Oda, K.
AU - Kawana, K.
AU - Katakura, Y.
AU - Yano, T.
AU - Masai, H.
AU - Roy, A. L.
AU - Osuga, Y.
AU - Fujii, T.
N1 - Funding Information:
This work was supported by Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture; JMS Bayer Schering Pharma Grant; Kowa Life Science Foundation; and Kanzawa Medical Research Foundation. We thank Dr RG Roeder (The Rockefeller University) for the TFII-I expression vectors.
PY - 2013/12/10
Y1 - 2013/12/10
N2 - 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.
AB - 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.
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U2 - 10.1038/bjc.2013.532
DO - 10.1038/bjc.2013.532
M3 - Article
C2 - 24231951
AN - SCOPUS:84890430889
SN - 0007-0920
VL - 109
SP - 3042
EP - 3048
JO - British journal of cancer
JF - British journal of cancer
IS - 12
ER -
