Dissimilar mispair‐recognition spectra of Arabidopsis DNA‐mismatch‐repair proteins MSH2·MSH6 (MutSα) and MSH2·MSH7 (MutSγ)
Dissimilar mispair‐recognition spectra of Arabidopsis DNA‐mismatch‐repair proteins MSH2·MSH6 (MutSα) and MSH2·MSH7 (MutSγ)
复制标题
DOI：
10.1093/nar/gkg780
复制
发表时间：
2003-10
影响因子：
14.9
通讯作者：
Shiau-Yin Wu;K. Culligan;M. Lamers;J. Hays
中科院分区：
文献类型：
--
作者：
Shiau-Yin Wu;K. Culligan;M. Lamers;J. Hays
除了其他真核错配修复（MMR）蛋白的直系同源物外，植物还编码MSH 7，MSH 6的一个同源物。拟南芥识别异二聚体AtMSH 2·MSH 6（AtMutSα）和AtMSH 2·MSH 3（AtMutSβ）之前被发现与其他真核生物中的对应物结合相同的错配子集-分别是碱基间错配和单个额外核苷酸，仅额外核苷酸的环出（一个或多个）-但AtMSH 2·MSH 7（AtMutSγ）仅与G/T错配结合良好。为了验证MSH 7可能专门针对G/T或5-甲基胞嘧啶背景下碱基错配的假设，我们比较了AtMutSα和AtMutSγ与一系列错配DNA寡聚体的结合，相对于它们与G/T DNA的结合（大致相似）。AtMutSγ结合G/G、G/A、A/A，尤其是C/A错配与G/T一样好或比G/T更好，与MutSα相反，G/T显然是最好的碱基错配。5-甲基胞嘧啶邻近或错配中的存在通常降低了两种异二聚体的结合，两者之间没有系统差异。蛋白质序列的比对揭示了在MSH 7中缺少在细菌MutS蛋白中的钳结构域，并且通过推断MSH 6蛋白非特异性地结合错配DNA的骨架，这就提出了关于钳结构域如何增强错配识别的新问题。植物必须严格抑制突变分生组织细胞的有丝分裂，最终产生配子，也可以使用MMR蛋白拮抗同源重组。MSH 6与MSH 7的差异可能反映了特定错配和/或序列背景的特化，以增加DNA复制和减数分裂重组保真度，或MSH 6对前者的贡献和MSH 7对后者的贡献，与小麦的遗传证据一致。
Besides orthologs of other eukaryotic mismatch-repair (MMR) proteins, plants encode MSH7, a paralog of MSH6. The Arabidopsis thaliana recognition heterodimers AtMSH2·MSH6 (AtMutSα) and AtMSH2·MSH3 (AtMutSβ) were previously found to bind the same subsets of mismatches as their counterparts in other eukaryotes—respectively, base–base mismatches and single extra nucleotides, loopouts of extra nucleotides (one or more) only—but AtMSH2·MSH7 (AtMutSγ) bound well only to a G/T mismatch. To test hypotheses that MSH7 might be specialized for G/T, or for base mismatches in 5-methylcytosine contexts, we compared binding of AtMutSα and AtMutSγ to a series of mismatched DNA oligoduplexes, relative to their (roughly similar) binding to G/T DNA. AtMutSγ bound G/G, G/A, A/A and especially C/A mispairs as well or better than G/T, in contrast to MutSα, for which G/T was clearly the best base mismatch. The presence of 5-methylcytosine adjacent to or in a mispair generally lowered binding by both heterodimers, with no systematic difference between the two. Alignment of protein sequences reveals the absence in MSH7 of the clamp domains that in bacterial MutS proteins—and by inference MSH6 proteins—non-specifically bind the backbone of mismatched DNA, raising new questions as to how clamp domains enhance mismatch recogni tion. Plants must rigorously suppress mutation during mitotic division of meristematic cells that eventually give rise to gametes and may also use MMR proteins to antagonize homeologous recombination. The MSH6 versus MSH7 divergence may reflect specializations for particular mismatches and/or sequence contexts, so as to increase both DNA-replication and meiotic-recombination fidelity, or dedication of MSH6 to the former and MSH7 to the latter, consistent with genetic evidence from wheat.