Fishel R, Ewel A, Lescoe M K
Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont School of Medicine, Burlington 05405.
Cancer Res. 1994 Nov 1;54(21):5539-42.
The human hMSH2 protein is a member of a highly conserved family of postreplication mismatch repair components found from bacteria to humans. Alterations of the gene coding for this protein cosegregate with, and are the likely cause of, chromosome 2-linked hereditary nonpolyposis colon cancer. Postreplication mismatch repair has been found to faithfully replace misincorporated nucleotides, thereby increasing the overall fidelity of DNA replication. Loss of postreplication mismatch repair function leads to a mutator phenotype, which is proposed to account for the multiple mutations required for multistep carcinogenesis. Although the functions of hMSH2 can be anticipated based on its similarity to well-characterized bacterial and yeast proteins, proof of its functions has not been established. Here we demonstrate that purified hMSH2 binds specifically to mismatched nucleotides, providing a target for the excision repair processes characteristic of postreplication mismatch repair.
人类hMSH2蛋白是一个高度保守的复制后错配修复成分家族的成员，该家族在从细菌到人类的生物中均有发现。编码此蛋白的基因改变与2号染色体连锁的遗传性非息肉病性结肠癌共分离，并且可能是其病因。已发现复制后错配修复能忠实地替换错配掺入的核苷酸，从而提高DNA复制的整体保真度。复制后错配修复功能的丧失导致突变表型，这被认为是多步骤致癌所需的多种突变的原因。尽管基于hMSH2与已充分表征的细菌和酵母蛋白的相似性可以预测其功能，但尚未证实其功能。在此，我们证明纯化的hMSH2特异性结合错配核苷酸，为复制后错配修复特有的切除修复过程提供了靶点。
