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Association of p53 and MSH2 with recombinative repair complexes during S phase

Oncogene volume 21, pages 4788–4800 (2002)Cite this article

A Corrigendum to this article was published on 09 May 2003

Abstract

Our previous recombination and biochemical analyses have led to the hypothesis that the tumor suppressor p53 monitors homologous recombination, a function which was previously attributed to the mismatch repair protein MSH2. Here, we show that a certain fraction of p53 is concentrated within discrete nuclear foci of cells synchronized in G1 phase, a pattern which becomes even more pronounced in S phase, especially after γ-ray treatment. p53 foci show some colocalization with MSH2 within distinct foci during G1 phase, while dots formed by BRCA1 display an independent localization pattern. In S phase nuclei, p53 foci almost completely colocalize with MSH2 foci and associate with the recombination surveillance factor BRCA1 in irradiated S phase cells. These p53 and MSH2 foci also show significant overlaps with foci of the recombination enzymes Rad50 and Rad51, which for the first time unveiled recombination-related functions of p53 in replicating cells. During S phase, p53 and MSH2 are maximally active in binding to early recombination intermediates, and coexist within the same nuclear DNA-protein complexes. Our data suggest that p53 is linked similarly to homologous recombination as MSH2 and provide further evidence for the new concept of a dual role of p53 in the regulation of growth and repair.

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Acknowledgements

We are especially indebted to Prof Dr John HJ Petrini, University of Wisconsin Medical School, Madison, and to Akira Shinohara, Osaka University, for supplying Rad50 and Rad51 antiserum, respectively. We thank Evelyn Bendrat for excellent technical assistance. This work was supported by the Deutsche Forschungsgemeinschaft, grants Wi 1376/1-4 and -5 and grant 10-1281-Wi I by the Deutsche Krebshilfe, the Dr Mildred Scheel Stiftung.

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  1. Institut für Anthropologie und Humangenetik LMU München, Goethestr, 31,80336, München, Germany

    Daniele Zink & Christoph Mayr

  2. Universitätsfrauenklinik und Poliklinik, Prittwitzstrasse 43, Ulm, D-89075, Germany

    Christine Janz & Lisa Wiesmüller

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  1. Daniele Zink
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Correspondence to Christine Janz.

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Zink, D., Mayr, C., Janz, C. et al. Association of p53 and MSH2 with recombinative repair complexes during S phase. Oncogene 21, 4788–4800 (2002). https://doi.org/10.1038/sj.onc.1205614

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Keywords

  • BRCA1-associated surveillance complex
  • Rad50
  • Rad51
  • replication-associated homologous recombination
  • tumor suppressor

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