Prolla T A, Pang Q, Alani E, Kolodner R D, Liskay R M
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06511.
Science. 1994 Aug 19;265(5175):1091-3. doi: 10.1126/science.8066446.
The discovery that mutations in DNA mismatch repair genes can cause hereditary nonpolyposis colorectal cancer has stimulated interest in understanding the mechanism of DNA mismatch repair in eukaryotes. In the yeast Saccharomyces cerevisiae, DNA mismatch repair requires the MSH2, MLH1, and PMS1 proteins. Experiments revealed that the yeast MLH1 and PMS1 proteins physically associate, possibly forming a heterodimer, and that MLH1 and PMS1 act in concert to bind a MSH2-heteroduplex complex containing a G-T mismatch. Thus, MSH2, MLH1, and PMS1 are likely to form a ternary complex during the initiation of eukaryotic DNA mismatch repair.
DNA错配修复基因中的突变可导致遗传性非息肉病性结直肠癌，这一发现激发了人们对真核生物中DNA错配修复机制的研究兴趣。在酿酒酵母中，DNA错配修复需要MSH2、MLH1和PMS1蛋白。实验表明，酵母MLH1和PMS1蛋白在物理上相互关联，可能形成异源二聚体，并且MLH1和PMS1协同作用以结合含有G-T错配的MSH2-异源双链体复合物。因此，在真核生物DNA错配修复起始过程中，MSH2、MLH1和PMS1可能形成三元复合物。
