1. ¹Department of Dermatology, The Saarland University Hospital, Homburg, Germany
2. ²Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York, USA
3. ³Department of Dermatology and the Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University of Münster, Münster, Germany
4. ⁴Institute of Radiobiology, Federal Armed Forces Medical Academy, Munich; Germany
5. ⁵Department of Biophysics, The Saarland University Hospital, Homburg, Germany

Correspondence: Dr Markus Seifert, Department of Dermatology, The Saarland University Hospital 66421 Homburg/Saar, Germany. E-mail: hgmsei@uniklinik-saarland.de

Received 10 July 2006; Revised 24 January 2007; Accepted 18 March 2007; Published online 5 July 2007.

Abstract

The mechanisms by which the post-replicative DNA mismatch repair (MMR) enzyme MSH2 is involved in the complex response mechanisms to UV damage are yet to be clarified. Here, we show increased levels of MSH2 mRNA in malignant melanoma, metastases of melanoma, and melanoma cell (MeWo) lines as compared with melanocytic nevi or primary cultured benign melanocytes. UV-B treatment modulated MSH2 expression and silencing of MSH2 gene expression using small interfering RNA technology regulated UV-B-induced cell cycle arrest and apoptosis in human MeWo. We show that MSH2-deficient non-malignant mouse fibroblasts (MEF-/-) are partially resistant against UV-B-induced apoptosis and show reduced S-Phase accumulation. In addition, we show that an Msh2 point mutation (MEFGA) that affects MMR does not affect UV-B-induced apoptosis. In conclusion, we demonstrate that MSH2 modulates in human melanocytes both UV-B-induced cell cycle regulation and apoptosis, most likely via independent, uncoupled mechanisms.