Sonneveld E, Vrieling H, Mullenders L H, van Hoffen A
Department of Cell Biology and Genetics-MGC, Erasmus University Rotterdam, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Oncogene. 2001 Jan 25;20(4):538-41. doi: 10.1038/sj.onc.1204125.
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.
人类MutS同源基因MSH2对DNA错配修复（MMR）至关重要，该基因的缺陷会导致诱变增加、基因组不稳定和遗传性非息肉病性结直肠癌（HNPCC）。除了纠正DNA复制产生的错配错误外，研究表明包括MSH2在内的细菌和人类MMR基因缺陷会导致紫外线诱导的光损伤的转录偶联修复（TCR）缺陷。在这里，我们表明，来自两个具有明确Msh2缺陷的独立同基因小鼠品系的MMR缺陷成纤维细胞在紫外线诱导的环丁烷嘧啶二聚体（CPD）的TCR方面与野生型成纤维细胞一样熟练。我们的结果表明，与细菌和人类细胞相比，在小鼠细胞中Msh2对紫外线诱导的CPD的TCR不是必需的，并表明紫外线在小鼠Msh2（-/-）细胞和小鼠中的生物学效应不是由于TCR缺陷。
