(CAG)n-hairpin DNA binds to Msh2-Msh3 and changes properties of mismatch recognition
(CAG)n-hairpin DNA binds to Msh2-Msh3 and changes properties of mismatch recognition
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DOI：
10.1038/nsmb965
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发表时间：
2005-08-01
影响因子：
16.8
通讯作者：
McMurray, CT
中科院分区：
文献类型：
--
作者：
Owen, BAL;Yang, ZY;McMurray, CT
细胞已经进化出复杂的DNA修复系统来纠正受损的DNA。然而，人类DNA错配修复蛋白Msh2-Msh3参与了三核苷酸（CNG） DNA扩增而不是修复的过程。使用纯化蛋白和合成DNA底物，我们发现Msh2-Msh3与cag -发夹DNA结合，cag -发夹DNA是扩增中间体的主要候选物。cag -发夹结合抑制Msh2-Msh3的ATP酶活性，改变核苷酸（ADP和ATP）亲和力和蛋白质与DNA之间的结合界面。Msh2-Msh3功能的这些变化取决于发夹茎中A中心点A错配碱基的存在以及发夹DNA结构本身。这些研究确定了Msh2-Msh3-CAG发夹复合体中可能误导DNA修复过程的关键功能缺陷。
Cells have evolved sophisticated DNA repair systems to correct damaged DNA. However, the human DNA mismatch repair protein Msh2-Msh3 is involved in the process of trinucleotide (CNG) DNA expansion rather than repair. Using purified protein and synthetic DNA substrates, we show that Msh2-Msh3 binds to CAG-hairpin DNA, a prime candidate for an expansion intermediate. CAG-hairpin binding inhibits the ATPase activity of Msh2-Msh3 and alters both nucleotide (ADP and ATP) affinity and binding interfaces between protein and DNA. These changes in Msh2-Msh3 function depend on the presence of A center dot A mispaired bases in the stem of the hairpin and on the hairpin DNA structure per se. These studies identify critical functional defects in the Msh2-Msh3-CAG hairpin complex that could misdirect the DNA repair process.