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  • Original Paper
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Ku80 can translocate to the nucleus independent of the translocation of Ku70 using its own nuclear localization signal

Oncogene volume 18, pages 7495–7505 (1999)Cite this article

Abstract

Ku antigen is a complex of Ku70 and Ku80 subunits and plays an important role in not only DNA double-strand breaks (DSB) repair and V(D)J recombination, but also in growth regulation. Ku is generally believed to always form and function as heterodimers on the basis of in vitro observations. Here we demonstrate that the localization of Ku80 does not completely coincide with that of Ku70. Ku70 and Ku80 were colocalized in the nucleus in the interphase but not in the late telophase/early G1 phase of the cell cycle. Since the in vivo function of Ku might be partially regulated by the control of its transport, we attempted to investigate the molecular mechanisms underlying the nuclear translocation of Ku. The nuclear translocation of Ku80 started during the late telophase/early G1 phase after the nuclear envelope was formed and this was preceded by the nuclear translocation of Ku70. Furthermore, we found that the Ku80 protein was transported to the nucleus without heterodimerization with Ku70. To understand in detail the mechanism of transport of Ku80, we attempted to identify the nuclear localization signal (NLS) of Ku80 and defined to a region spanning nine amino acid residues (positions 561 – 569). The Ku80 NLS was demonstrated to be mediated to the nuclear rim by two components of PTAC58 and PTAC97. All these findings support the idea that Ku80 can translocate to the nucleus using its own NLS independent of the translocation of Ku70.

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Acknowledgements

We thank Dr T Mimori for providing us with the Ku cDNA and human anti-Ku serum (OM). We also thank Dr T Tachibana and Dr Y Yoneda for providing the GST-GFP2 vector, the GST-NLSc-GFP vector, PTAC58 cDNA, PTAC97 cDNA and helpful advice. We thank Dr K Kawajiri and members of his laboratory for their encouragement and helpful discussion. We are particularly grateful to Dr T Awaji for his assistance in obtaining the confocal images and Y Kiyomatsu of Olympus Japan Co. Ltd. for his excellent technical assistance with the LSC analysis. This work was supported in part by grants from the Science and Technology Agency and from the Ministry of Education, Science, Sports, and Culture, Japan.

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  1. Genome Research Group, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan

    Manabu Koike, Takashi Miyasaka & Tadahiro Shiomi

  2. Saitama Cancer Center Research Institute, 818 Komuro, Ina-machi, Kitaadachi-gun, 362-0806, Saitama, Japan

    Togo Ikuta

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Koike, M., Ikuta, T., Miyasaka, T. et al. Ku80 can translocate to the nucleus independent of the translocation of Ku70 using its own nuclear localization signal. Oncogene 18, 7495–7505 (1999). https://doi.org/10.1038/sj.onc.1203247

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