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The Nijmegen breakage syndrome gene and its role in genome stability

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Abstract

NBS1 is the key regulator of the RAD50/MRE11/NBS1 (R/M/N) protein complex, a sensor and mediator for cellular DNA damage response. NBS1 potentiates the enzymatic activity of MRE11 and directs the R/M/N complex to sites of DNA damage, where it forms nuclear foci by interacting with phosphorylated H2AX. The R/M/N complex also activates the ATM kinase, which is a major kinase involved in the activation of DNA damage signal pathways. The ATM requires the R/M/N complex for its own activation following DNA damage, and for conformational change to develop a high affinity for target proteins. In addition, association of NBS1 with PML, the promyelocytic leukemia protein, is required to form nuclear bodies, which have various functions depending on their location and composition. These nuclear bodies function not only in response to DNA damage, but are also involved in telomere maintenance when they are located on telomeres. In this review, we describe the role of NBS1 in the maintenance of genetic stability through the activation of cell-cycle checkpoints, DNA repair, and protein relocation.

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Acknowledgements

The authors thank Dr. Leon N. Kapp for his valuable comments and for editing the manuscript. This work was supported in part by a Grant-in-aid (Kaken-hi) from the Ministry of Education, Science, Sports and Culture of Japan; by a Research Grant from the Uehara Memorial Foundation; and a grant from the Research Project Fund for “Studies on the Molecular Biological Basis of Low-Dose Radiation Effects” from the Japan Atomic Energy Research Institute through a contract with the Nuclear Safety Research Association.

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Authors and Affiliations

  1. Department of Environmental Sciences, Faculty of Science, Ibaraki University, Bunkyo 2-1-1, Mito, Ibaraki, 310-8512, Japan

    Kenta Iijima & Hiroshi Tauchi

  2. Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Yoshida-Konoe, Sakyo-ku, Kyoto, 606-8501, Japan

    Kenshi Komatsu

  3. Department of Radiation Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8553, Japan

    Shinya Matsuura

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  1. Kenta Iijima
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  2. Kenshi Komatsu
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  3. Shinya Matsuura
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  4. Hiroshi Tauchi
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Correspondence to Hiroshi Tauchi.

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Communicated by E.A. Nigg

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Iijima, K., Komatsu, K., Matsuura, S. et al. The Nijmegen breakage syndrome gene and its role in genome stability. Chromosoma 113, 53–61 (2004). https://doi.org/10.1007/s00412-004-0298-0

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