Abstract
Microsatellite instability (MSI) secondary to replication errors can be detected in various malignant human epithelial and melanocytic skin tumors.1 Microsatellite instability is a recently recognized genetic mechanism important in the development of various human cancers that is characterized by length changes at repetitive loci scattered throughout the genome.2,3 In most patients with hereditary nonpolyposis colon cancer (HNPCC), where almost every tumour reveals a high incidence of mutations in microsatellite repeat sequences, it was shown that cancer predisposition is attributable to defects in any one of four genes, all of which encode homologs of the microbial mismatch repair proteins mutS and mutL.3,4 The hMSH-2 gene specifies a mutS homolog, whereas hMLH1, hPMS1, and hPMS2 encode homologs of mutL.5 Analysis of all the 16 exons of hMSH2 in 34 unrelated HNPCC kindreds has revealed a heterogeneous spectrum of mutations.3,6 Tumour cells that display microsatellite instability are typically defective in mismatch correction, thus providing a direct link between DNA-mismatch repair enzymes and genetic stability afforded by this DNA repair system.7 Recently, we have cloned the promoter region of hMSH-2 and detected a site with homology to the p53 consensus binding sequence.8 Using gel mobility shift assays we were able to show that purified p53 has at least in vitro the potential to bind specifically the hMSH-2 motif.9
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Reichrath, J. et al. (1999). Expression of hMSH-2 Mismatch-Repair Gene in Epithelial and Melanocytic Skin Tumors: Regulation by P53 Protein and UV-B Irradiation. In: Holick, M.F., Jung, E.G. (eds) Biologic Effects of Light 1998. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5051-8_39
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DOI: https://doi.org/10.1007/978-1-4615-5051-8_39
Publisher Name: Springer, Boston, MA
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