Cell cycle regulation of the human DNA mismatch repair genes hMSH2, hMLH1, and hPMS2.
Cell cycle regulation of the human DNA mismatch repair genes hMSH2, hMLH1, and hPMS2.
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发表时间：
1997-01
期刊：
影响因子：
11.2
通讯作者：
M. Meyers;Maria Theodosiou;Samir Acharya;E. Odegaard;Teresa Wilson;Janet E. Lewis;Thomas W. Davis;Carmell Wilson Van Patten;Richard Fishel;D. Boothman
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作者：
M. Meyers;Maria Theodosiou;Samir Acharya;E. Odegaard;Teresa Wilson;Janet E. Lewis;Thomas W. Davis;Carmell Wilson Van Patten;Richard Fishel;D. Boothman
遗传性非息肉病性结直肠癌是一种癌症易感性综合征，已发现由参与DNA错配修复的几种基因中的任何一种突变引起，包括hMSH 2，hMLH 1或hPMS 2。最近的报道表明，hMSH 2和hMLH 1在细胞周期的调节中起作用。为了确定这些基因是否受细胞周期调控，我们在IMR-90正常人肺成纤维细胞中检测了它们在整个细胞周期中的mRNA和蛋白水平。我们证明，hMSH 2 mRNA和蛋白质的水平在整个细胞周期中没有明显的变化。虽然hMLH 1 mRNA水平保持不变，有一个温和的（约50%）增加，其蛋白水平在G1和S期后期。hPMS 2 mRNA水平波动（G1期下降50%，S期增加50%），而hPMS 2蛋白水平在G1晚期和S期增加50%。我们的数据表明，至少在正常细胞中，负责检测和修复错配DNA碱基的机制存在于整个细胞周期中。
Hereditary nonpolyposis colorectal cancer is a cancer susceptibility syndrome that has been found to be caused by mutations in any of several genes involved in DNA mismatch repair, including hMSH2, hMLH1, or hPMS2. Recent reports have suggested that hMSH2 and hMLH1 have a role in the regulation of the cell cycle. To determine if these genes are cell cycle regulated, we examined their mRNA and protein levels throughout the cell cycle in IMR-90 normal human lung fibroblasts. We demonstrate that the levels of hMSH2 mRNA and protein do not change appreciably throughout the cell cycle. Although hMLH1 mRNA levels remained constant, there was a modest (approximately 50%) increase in its protein levels during late G1 and S phase. The levels of hPMS2 mRNA fluctuated (decreasing 50% in G1 and increasing 50% in S phase), whereas hPMS2 protein levels increased 50% in late G1 and S phase. Our data indicate that, at least in normal cells, the machinery responsible for the detection and repair of mismatched DNA bases is present throughout the cell cycle.