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PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition

Oncogene volume 19, pages 5291–5297 (2000)Cite this article

Abstract

The hHus1 and several hRad proteins are involved in the control of DNA integrity checkpoints, although the mechanisms underlying these processes are unknown. Using a yeast two-hybrid system to detect protein-protein interactions, we found that human proliferating cell nuclear antigen (PCNA), a protein known to function in both DNA replication and repair, interacts with the human checkpoint-related protein Hus1 (hHus1). In human skin fibroblast cells, exposure to ionizing radiation of hydroxyurea triggers translocation of hHus1 from the cytosol to the nucleus, where it associates with PCNA as well as another checkpoint protein, hRad9. This nuclear translocation and the complex formation or hHus1 with PCNA and hRad9 correlate closely with changes in cell cycle distribution in response to radiation exposure. These results suggest that this multi-protein complex may be important for coordinating cell-cycle progression, DNA replication and repair of damaged DNA.

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Acknowledgements

We thank Nikola Valkov for assistance with fluorescence confocal microscopy, the Molecular Biology, Flow Cytometry and Molecular Imaging core facilities at the Moffitt Cancer Center and Research Institute, and the NIH (CA82197, CA72694, GM52493, and CA68446) for support.

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Authors and Affiliations

  1. Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, 33612, Florida, FL, USA

    Kiyoshi Komatsu & Hong-Gang Wang

  2. Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, 33612, Florida, FL, USA

    Walker Wharton & W J Pledger

  3. Center for Radiological Research, Columbia University, 630 West 168th Street, New York, 10032, NY, USA

    Haiying Hang & Howard B Lieberman

  4. Imgenex Corporation, 11175 Flintkote Avenue, San Diego, 92121, California, CA, USA

    Chun Wu & Sujay Singh

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  1. Kiyoshi Komatsu
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  2. Walker Wharton
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  4. Chun Wu
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Komatsu, K., Wharton, W., Hang, H. et al. PCNA interacts with hHus1/hRad9 in response to DNA damage and replication inhibition. Oncogene 19, 5291–5297 (2000). https://doi.org/10.1038/sj.onc.1203901

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