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Disruption of B-myb in DT40 cells reveals novel function for B-Myb in the response to DNA-damage

Abstract

B-Myb is a highly conserved vertebrate member of the Myb transcription factor family, which is expressed in virtually all proliferating cells. A large body of evidence suggests that B-Myb plays an important role in cell cycle regulation; however, the exact nature of its function has not yet been clarified. We have used gene targeting in chicken DT40 cells, a cell line exhibiting very high rates of homologous recombination, to create cells expressing endogenous B-myb in a doxycyclin-dependent manner. We find that the cells proliferate well in the absence of B-Myb, suggesting that B-Myb is not essential for cell proliferation per se. However, cells lacking B-Myb are more sensitive to DNA-damage induced by UV-irradiation and alkylation. Our work provides the first direct evidence for a novel function of B-Myb in the response to DNA-damage. The cells described here should be a useful model to characterize this function in more detail.

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Acknowledgements

We thank D Wenning for excellent technical assistance and J Delrow and the staff of the microarray facility of the Fred Hutchinson Cancer Research Center for performing the microarray experiments. This work was supported by the DFG (KL461/9-2).

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Correspondence to Karl-Heinz Klempnauer.

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Ahlbory, D., Appl, H., Lang, D. et al. Disruption of B-myb in DT40 cells reveals novel function for B-Myb in the response to DNA-damage. Oncogene 24, 7127–7134 (2005). https://doi.org/10.1038/sj.onc.1208869

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Keywords

  • B-myb
  • DT40
  • homologous recombination
  • DNA-damage

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