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Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1

Pedrazzi, Graziella ; Perrera, Claudia ; Blaser, Heiko ; Kuster, Patrick ; Marra, Giancarlo ; Davies, Sally L. ; Ryu, Gi-Hyuck ; Freire, Raimundo ; Hickson, Ian D. ; Jiricny, Josef ; Stagljar, Igor

In: Nucleic Acids Research, 2001, vol. 29, no. 21, p. 4378-4386

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    Title
    • Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1
    Author
    • Pedrazzi, Graziella
    • Perrera, Claudia. Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, Institute of Medical Radiobiology of the University of Zürich and the Paul Scherrer Institute, August Forel-Strasse 7, CH-8008 Zürich, Switzerland, Imperial Cancer Research Fund Laboratiories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK and Unidad de Investigacion, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38071 Tenerife, Spain
    • Blaser, Heiko
    • Kuster, Patrick
    • Marra, Giancarlo. Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, Institute of Medical Radiobiology of the University of Zürich and the Paul Scherrer Institute, August Forel-Strasse 7, CH-8008 Zürich, Switzerland, Imperial Cancer Research Fund Laboratiories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK and Unidad de Investigacion, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38071 Tenerife, Spain
    • Davies, Sally L.. Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, Institute of Medical Radiobiology of the University of Zürich and the Paul Scherrer Institute, August Forel-Strasse 7, CH-8008 Zürich, Switzerland, Imperial Cancer Research Fund Laboratiories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK and Unidad de Investigacion, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38071 Tenerife, Spain
    • Ryu, Gi-Hyuck
    • Freire, Raimundo. Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, Institute of Medical Radiobiology of the University of Zürich and the Paul Scherrer Institute, August Forel-Strasse 7, CH-8008 Zürich, Switzerland, Imperial Cancer Research Fund Laboratiories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK and Unidad de Investigacion, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38071 Tenerife, Spain
    • Hickson, Ian D.. Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, Institute of Medical Radiobiology of the University of Zürich and the Paul Scherrer Institute, August Forel-Strasse 7, CH-8008 Zürich, Switzerland, Imperial Cancer Research Fund Laboratiories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK and Unidad de Investigacion, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38071 Tenerife, Spain
    • Jiricny, Josef. Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, Institute of Medical Radiobiology of the University of Zürich and the Paul Scherrer Institute, August Forel-Strasse 7, CH-8008 Zürich, Switzerland, Imperial Cancer Research Fund Laboratiories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK and Unidad de Investigacion, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38071 Tenerife, Spain
    • Stagljar, Igor
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Nucleic Acids Research, 2001, vol. 29, no. 21, p. 4378-4386. Oxford University Press
    Other Version
    Classification
    • Health
    OAI-PMH Identifier
    • oai:doc.rero.ch:297825
    Summary
    Bloom's syndrome (BS) is a rare genetic disorder characterised by genomic instability and cancer susceptibility. BLM, the gene mutated in BS, encodes a member of the RecQ family of DNA helicases. Here, we identify hMLH1, which is involved in mismatch repair (MMR) and recombination, as a protein that directly interacts with BLM both in vivo and in vitro, and that the two proteins co-localise to discrete nuclear foci. The interaction between BLM and hMLH1 appears to have been evolutionarily conserved, as Sgs1p, the Saccharomyces cerevisiae homologue of BLM, interacts with yeast Mlh1p. However, cell extracts derived from BS patients show no obvious defects in MMR compared to wild-type- and BLM-complemented BS cell extracts. We conclude that the hMLH1-BLM interaction is not essential for post-replicative MMR, but, more likely, is required for some aspect of genetic recombination