（CAG）（n）-发夹DNA与Msh2-Msh3结合并改变错配识别特性。
(CAG)(n)-hairpin DNA binds to Msh2-Msh3 and changes properties of mismatch recognition.
作者信息
Owen Barbara A L, Yang Zungyoon, Lai Maoyi, Gajec Maciej, Badger John D, Hayes Jeffrey J, Edelmann Winfried, Kucherlapati Raju, Wilson Teresa M, McMurray Cynthia T
机构信息
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic Rochester, Rochester, Minnesota 55905, USA.
出版信息
Nat Struct Mol Biol. 2005 Aug;12(8):663-70. doi: 10.1038/nsmb965. Epub 2005 Jul 17.
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.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.
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 - Msh3参与三核苷酸（CNG）DNA扩增过程而非修复过程。使用纯化的蛋白质和合成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发夹结合会抑制Msh2 - Msh3的ATP酶活性，并改变核苷酸（ADP和ATP）亲和力以及蛋白质与DNA之间的结合界面。Msh2 - Msh3功能的这些变化取决于发夹茎中错配碱基A的存在以及发夹DNA结构本身。这些研究确定了Msh2 - Msh3 - CAG发夹复合物中的关键功能缺陷，这些缺陷可能会误导DNA修复过程。
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