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  • Original Paper
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The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase

Oncogene volume 23, pages 3749–3756 (2004)Cite this article

Abstract

The human MSH2/6 complex is essential for mismatch recognition during the repair of replication errors. Although mismatch repair components have been implicated in DNA homologous recombination repair, the exact function of hMSH2/6 in this pathway is unclear. Here, we show that the recombinant hMSH2/6 protein complex stimulated the ability of the Bloom's syndrome gene product, BLM, to process Holliday junctions in vitro, an activity that could also be regulated by p53. Consistent with these observations, hMSH6 colocalized with BLM and phospho-ser15-p53 in hydroxyurea-induced RAD51 nuclear foci that may correspond to the sites of presumed stalled DNA replication forks and more likely the resultant DNA double-stranded breaks. In addition, we show that hMSH2 and hMSH6 coimmunoprecipitated with BLM, p53, and RAD51. Both the number of RAD51 foci and the amount of the BLM–p53–RAD51 complex are increased in hMSH2- or hMSH6-deficient cells. These data suggest that hMSH2/6 formed a complex with BLM–p53–RAD51 in response to the damaged DNA forks during double-stranded break repair.

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Acknowledgements

This work was supported, in part, by Grants GM45190 (to PM); IDH was supported by Cancer Research UK. We thank Dorothea Dudek and the NCI, CCR, Fellows Editorial Board for their editorial assistance.

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Authors and Affiliations

  1. Laboratory of Human Carcinogenesis, National Cancer Institute, NIH, Bldg 37, Rm 3068, 37 Convent Drive, Bethesda, 20892-4255, MD, USA

    Qin Yang, Ran Zhang, Xin W Wang, Steven P Linke, Sagar Sengupta & Curtis C Harris

  2. John Radcliffe Hospital, Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK

    Ian D Hickson

  3. Institute of Vet. Biochemistry and Molecular Biology, University of Zurich-Irchel, Switzerland

    Graziella Pedrazzi & Igor Stagljar

  4. Institute of Molecular Cancer Research, University of Zurich, Switzerland

    Claudia Perrera

  5. Department of Medicine, Duke Medical Center, Durham, 27710, NC, USA

    Susan J Littman

  6. Department Biochemistry, Howard Hughes Medical Institute, Duke Medical Center, Box 3711, Durham, 27710, NC, USA

    Paul Modrich

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  1. Qin Yang
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Correspondence to Curtis C Harris.

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Yang, Q., Zhang, R., Wang, X. et al. The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase. Oncogene 23, 3749–3756 (2004). https://doi.org/10.1038/sj.onc.1207462

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