The DNA-mismatch repair enzyme hMSH2 modulates UV-B-induced cell cycle arrest and apoptosis in melanoma cells

Markus Seifert, Stefan J. Scherer, Winfried Edelmann, Markus Böhm, Viktor Meineke, Markus Löbrich, Wolfgang Tilgen, Jörg Reichrath

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)203-213
Number of pages11
JournalJournal of Investigative Dermatology
Volume128
Issue number1
DOIs
StatePublished - Jan 2008

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DNA Repair Enzymes
DNA Mismatch Repair
Cell Cycle Checkpoints
Melanoma
Repair
Cells
Apoptosis
Melanocytes
DNA
Enzymes
Pigmented Nevus
Fibroblasts
S Phase
Point Mutation
Gene expression
Small Interfering RNA
Cell Cycle
Neoplasm Metastasis
Technology
Gene Expression

ASJC Scopus subject areas

  • Dermatology

Cite this

The DNA-mismatch repair enzyme hMSH2 modulates UV-B-induced cell cycle arrest and apoptosis in melanoma cells. / Seifert, Markus; Scherer, Stefan J.; Edelmann, Winfried; Böhm, Markus; Meineke, Viktor; Löbrich, Markus; Tilgen, Wolfgang; Reichrath, Jörg.

In: Journal of Investigative Dermatology, Vol. 128, No. 1, 01.2008, p. 203-213.

Research output: Contribution to journalArticle

Seifert, Markus ; Scherer, Stefan J. ; Edelmann, Winfried ; Böhm, Markus ; Meineke, Viktor ; Löbrich, Markus ; Tilgen, Wolfgang ; Reichrath, Jörg. / The DNA-mismatch repair enzyme hMSH2 modulates UV-B-induced cell cycle arrest and apoptosis in melanoma cells. In: Journal of Investigative Dermatology. 2008 ; Vol. 128, No. 1. pp. 203-213.
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