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Nucleic Acids Research, 2001, Vol. 29, No. 21 4378-4386
© 2001 Oxford University Press

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

Graziella Pedrazzi, Claudia Perrera1, Heiko Blaser, Patrick Kuster, Giancarlo Marra1, Sally L. Davies2, Gi-Hyuck Ryu, Raimundo Freire3, Ian D. Hickson2, Josef Jiricny1 and Igor Stagljar*

Institute of Veterinary Biochemistry and Molecular Biology, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland, 1Institute of Medical Radiobiology of the University of Zürich and the Paul Scherrer Institute, August Forel-Strasse 7, CH-8008 Zürich, Switzerland, 2Imperial Cancer Research Fund Laboratiories, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK and 3Unidad de Investigacion, Hospital Universitario de Canarias, Ofra s/n, La Cuesta, 38071 Tenerife, Spain

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.

* To whom correspondence should be addressed. Tel: +41 1 635 54 74; Fax: +41 1 635 68 40; Email: stagljar{at}vetbio.unizh.ch Present address:Gi-Hyuck Ryu, Sungkyunkwan University School of Medicine, 300 Chunchun-Dong, Changan-Ku, Suwon, Kyunggi 440-746, Korea


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