Scherer S J, Welter C, Zang K D, Dooley S
Department of Human Genetics, University of Saarland, Homburg, Germany.
Biochem Biophys Res Commun. 1996 Apr 25;221(3):722-8. doi: 10.1006/bbrc.1996.0663.
MSH2 is one of the genes involved in DNA-mismatch repair. Mutations in the coding region of the human gene (hMSH2) have been shown to be directly involved in microsatellite instability in hereditary nonpolyposis colorectal tumors. Examination of the promoter region of hMHS2 revealed a site with homology to the p53 consensus binding sequence. Using gel mobility shift experiments we were able to show that purified p53 has at least in vitro the potential to specifically bind the hMSH2-p53 motif. This binding activity was even stronger than the binding activity measured with the p53-consensus site. These data identify the hMSH2 gene as a possible novel p53-regulated target gene and indicate a direct involvement of p53 in repair mechanisms via DNA binding of a mismatch repair gene.
MSH2是参与DNA错配修复的基因之一。人类基因（hMSH2）编码区的突变已被证明直接参与遗传性非息肉病性结直肠癌中的微卫星不稳定性。对hMHS2启动子区域的检查揭示了一个与p53共有结合序列具有同源性的位点。通过凝胶迁移率变动实验，我们能够证明纯化的p53至少在体外具有特异性结合hMSH2 - p53基序的潜力。这种结合活性甚至比用p53共有位点测得的结合活性更强。这些数据将hMSH2基因确定为一个可能的新型p53调节靶基因，并表明p53通过错配修复基因的DNA结合直接参与修复机制。
