Wiesendanger M, Kneitz B, Edelmann W, Scharff M D
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
J Exp Med. 2000 Feb 7;191(3):579-84. doi: 10.1084/jem.191.3.579.
Although the primary function of the DNA mismatch repair (MMR) system is to identify and correct base mismatches that have been erroneously introduced during DNA replication, recent studies have further implicated several MMR components in somatic hypermutation of immunoglobulin (Ig) genes. We studied the immune response in mice deficient in MutS homologue (MSH)3 and MSH6, two mutually exclusive partners of MSH2 that have not been examined previously for their role in Ig hypermutation. In Msh6(-)/- and Msh3(-)/-/Msh6(-)/- mice, base substitutions are preferentially targeted to G and C nucleotides and to an RGYW hot spot, as has been shown previously in Msh2(-)/- mice. In contrast, Msh3(-)/- mice show no differences from their littermate controls. These findings indicate that the MSH2-MSH6 heterodimer, but not the MSH2-MSH3 complex, is responsible for modulating Ig hypermutation.
尽管DNA错配修复（MMR）系统的主要功能是识别并纠正DNA复制过程中错误引入的碱基错配，但最近的研究进一步表明，几种MMR成分参与了免疫球蛋白（Ig）基因的体细胞超突变。我们研究了MutS同源物（MSH）3和MSH6缺陷小鼠的免疫反应，MSH3和MSH6是MSH2的两个相互排斥的伙伴，此前尚未研究它们在Ig超突变中的作用。在Msh6(-)/-和Msh3(-)/-/Msh6(-)/-小鼠中，碱基替换优先靶向G和C核苷酸以及RGYW热点，这与之前在Msh2(-)/-小鼠中观察到的情况一致。相比之下，Msh3(-)/-小鼠与同窝对照没有差异。这些发现表明，负责调节Ig超突变的是MSH2-MSH6异二聚体，而非MSH2-MSH3复合物。
