Journal
BRITISH JOURNAL OF CANCER
Volume 109, Issue 12, Pages 3042-3048Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2013.532
Keywords
TFII-I; DBC1; cell cycle; DNA damage repair; homologous recombination; transcription factor
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Funding
- Ministry of Education, Science, and Culture
- JMS Bayer Schering Pharma Grant
- Kowa Life Science Foundation
- Kanzawa Medical Research Foundation
- Grants-in-Aid for Scientific Research [23657081, 23592437, 23570243] Funding Source: KAKEN
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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-gamma H2AX 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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