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Mouse mismatch repair gene Msh2 is not essential for transcription-coupled repair of UV-induced cyclobutane pyrimidine dimers

Abstract

The human mutS homolog gene MSH2 is essential for DNA mismatch repair (MMR) and defects in this gene can result in increased mutagenesis, genomic instability and hereditary nonpolyposis colorectal cancer (HNPCC). Besides correcting mismatch errors arising from DNA replication, it was shown that deficiencies in bacterial and human MMR genes including MSH2 resulted in defective transcription-coupled repair (TCR) of UV-induced photolesions. Here we show that MMR-deficient fibroblasts derived from two independent isogenic mouse strains with defined Msh2 deficiencies are as proficient in TCR of UV-induced cyclobutane pyrimidine dimers (CPD) as wildtype fibroblasts. Our results indicate that in mouse cells Msh2 is not essential for TCR of UV-induced CPD in contrast to bacteria and human cells and suggest that the biological effects of UV in mouse Msh2−/− cells and mice are not due to defective TCR.

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Acknowledgements

The MEFs and the Msh2 antibody used in this study were obtained from Dr N de Wind, MGC-Department of Radiation Genetics and Chemical Mutagenesis, Leiden University Medical Center, Leiden, The Netherlands. Msh2Δ7N mice were obtained from Dr R Fodde, MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands. The authors thank Dr MPG Vreeswijk for expert technical assistance and Dr N de Wind for critical reading of the manuscript. This work was supported by Dutch Cancer Society Grants UU 97-1531 and EUR 98-1800.

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Sonneveld, E., Vrieling, H., Mullenders, L. et al. Mouse mismatch repair gene Msh2 is not essential for transcription-coupled repair of UV-induced cyclobutane pyrimidine dimers. Oncogene 20, 538–541 (2001). https://doi.org/10.1038/sj.onc.1204125

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