Strand M, Earley M C, Crouse G F, Petes T D
Department of Biology, University of North Carolina, Chapel Hill 27599-3280, USA.
Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10418-21. doi: 10.1073/pnas.92.22.10418.
Eukaryotic genomes contain tracts of DNA in which a single base or a small number of bases are repeated (microsatellites). Mutations in the yeast DNA mismatch repair genes MSH2, PMS1, and MLH1 increase the frequency of mutations for normal DNA sequences and destabilize microsatellites. Mutations of human homologs of MSH2, PMS1, and MLH1 also cause microsatellite instability and result in certain types of cancer. We find that a mutation in the yeast gene MSH3 that does not substantially affect the rate of spontaneous mutations at several loci increases microsatellite instability about 40-fold, preferentially causing deletions. We suggest that MSH3 has different substrate specificities than the other mismatch repair proteins and that the human MSH3 homolog (MRP1) may be mutated in some tumors with microsatellite instability.
真核生物基因组包含DNA片段，其中单个碱基或少数碱基会重复出现（微卫星）。酵母DNA错配修复基因MSH2、PMS1和MLH1中的突变会增加正常DNA序列的突变频率，并使微卫星不稳定。MSH2、PMS1和MLH1的人类同源物的突变也会导致微卫星不稳定，并引发某些类型的癌症。我们发现，酵母基因MSH3中的一个突变，虽对几个位点的自发突变率没有实质性影响，但会使微卫星不稳定性增加约40倍，且优先导致缺失。我们认为，MSH3具有与其他错配修复蛋白不同的底物特异性，并且人类MSH3同源物（MRP1）可能在一些具有微卫星不稳定性的肿瘤中发生了突变。
