Iaccarino I, Palombo F, Drummond J, Totty N F, Hsuan J J, Modrich P, Jiricny J
Istituto de Richerche di Biologia Molecolare P. Angeletti, Pomezia, Italy.
Curr Biol. 1996 Apr 1;6(4):484-6. doi: 10.1016/s0960-9822(02)00516-x.
The process of post-replicative DNA-mismatch repair seems to be highly evolutionarily conserved. In Escherichia coli, DNA mismatches are recognized by the MutS protein. Homologues of the E. coli mutS and mutL mismatch-repair genes have been identified in other prokaryotes, as well as in yeast and mammals. Recombinant Saccharomyces cerevisiae MSH2 (MSH for MutS homologue) and human hMSH2 proteins have been shown to bind to mismatch-containing DNA in vitro. However, the physiological role of hMSH2 is unclear, as shown by the recent finding that the mismatch-binding factor hMutS alpha isolated from extracts of human cells is a heterodimer of hMSH2 and another member of the MSH family, GTBP. It has been reported that S. cerevisiae possesses a mismatch-binding activity, which most probably contains MSH2. We show here that, as in human cells, the S. cerevisiae binding factor is composed of MSH2 and a new functional MutS homologue, MSH6, identified by its homology to GTBP.
复制后DNA错配修复过程似乎在进化上高度保守。在大肠杆菌中，DNA错配由MutS蛋白识别。大肠杆菌mutS和mutL错配修复基因的同源物已在其他原核生物以及酵母和哺乳动物中被鉴定出来。重组酿酒酵母MSH2（MutS同源物的MSH）和人hMSH2蛋白已被证明在体外可与含错配的DNA结合。然而，hMSH2的生理作用尚不清楚，最近的一项发现表明，从人细胞提取物中分离出的错配结合因子hMutSα是hMSH2与MSH家族的另一个成员GTBP的异二聚体。据报道，酿酒酵母具有错配结合活性，其中很可能包含MSH2。我们在此表明，与人类细胞一样，酿酒酵母结合因子由MSH2和一个新的功能性MutS同源物MSH6组成，MSH6通过与GTBP的同源性得以鉴定。
