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Binding of double-strand breaks in DNA by human Rad52 protein

Nature volume 398, pages 728–731 (1999)Cite this article

Abstract

Double-strand breaks (DSBs) in DNA are caused by ionizing radiation. These chromosomal breaks can kill the cell unless repaired efficiently, and inefficient or inappropriate repair can lead to mutation, gene translocation and cancer1. Two proteins that participate in the repair of DSBs are Rad52 and Ku: in lower eukaryotes such as yeast, DSBs are repaired by Rad52-dependent homologous recombination, whereas vertebrates repair DSBs primarily by Ku-dependent non-homologous end-joining2. The contribution of homologous recombination to vertebrate DSB repair, however, is important3,4. Biochemical studies indicate that Ku binds to DNA ends and facilitates end-joining5. Here we show that human Rad52, like Ku, binds directly to DSBs, protects them from exonuclease attack and facilitates end-to-end interactions. Amodel for repair is proposed in which either Ku or Rad52 binds the DSB. Ku directs DSBs into the non-homologous end-joining repair pathway, whereas Rad52 initiates repair by homologous recombination. Ku and Rad52, therefore, direct entry into alternative pathways for the repair of DNA breaks.

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Figure 1: DNA end-binding and end-to-end interactions promoted by hRad52.
Figure 2: Stimulation of DNA ligation by hRad52.
Figure 3: DNA-end protection by hRad52 protein.
Figure 4: Model for the initiation of double-strand break repair.

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Acknowledgements

We thank our colleagues for their interest, suggestions and careful reading of the manuscript. We also thank J. Dubochet for his interest in the project, and N. Hajibagheri for related electron microscopic analyses. This work was supported by the Imperial Cancer Research Fund, the Human Frontiers Science Program, the Swiss National Foundation and the Swiss-British Council Joint Research Program. E.V.D. was supported in part by an EC fellowship.

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Authors and Affiliations

  1. Imperial Cancer Research Fund, Clare Hall Laboratories, South Mimms, EN6 3LD, Herts, UK

    Eric Van Dyck & Stephen C. West

  2. Laboratoire d'Analyse Ultrastructurale, Universit de Lausanne, Lausanne-Dorigny, CH-1015, Switzerland

    Alicja Z. Stasiak & Andrzej Stasiak

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  1. Eric Van Dyck
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Correspondence to Stephen C. West.

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Dyck, E., Stasiak, A., Stasiak, A. et al. Binding of double-strand breaks in DNA by human Rad52 protein. Nature 398, 728–731 (1999). https://doi.org/10.1038/19560

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