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Nucleic Acids Research, 1994, Vol. 22, No. 25 5723-5728
© 1994


Articles

Cloning and expression of the Xenopus and mouse Msh2 DNA mismatch repair genes

Isabelle Varlet+,*, Caroline Pallard, Miroslav Radman, Jacques Moreau and Niels de Wind§

Laboratoire de Mutagenese, CNRS, Institut Jacques Monod Tour 43, 2 Place Jussieu, 75251 Paris cedex 05, France

*To whom correspondence should be addressed

+Present addresses: INSERM U 273, Centre de Biochimie, Univershe de Nice-Sophia Amipolis, Pare Valrose, 06108 Nice cedex 02, France

§Present addresses: Division of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

Received July 27, 1994. Revised November 14, 1994. Accepted November 14, 1994.

Bacterial MutS protein and its yeast and human homologs MSH2 trigger the mismatch repair process by their initial binding to mlspaired and unpaired bases In DNA. We describe the cloning and sequencing of genes from Xenopus laevls and Mus musculus encoding the homolog of the Saccharomyces cerevlslae MSH2 (the major DNA mismatch binding protein). Mutations in the human homolog of this gene have recently been Implicated In microsatelllte instability and DNA mismatch repair deficiency In tumour cells from patients with the most common hereditary predisposition to cancer (Lynch syndrome, or hereditary non-polyposis colorectal cancer, HNPCC), as well as In a significant percentage of sporadic tumours. Expression of the amphibian and murine Msh2 gene In different tissues appears to be ubiquitous. The Xenopus gene is highly expressed in eggs, a model system for the biochemistry of DNA mismatch repair. Expression of the murine gene Is low In all tissues examined, and Is relatively high In a rapidly dividing cell line. These data are suggestive of a role for MSH2 during DNA replication.


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