Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice
Altered somatic hypermutation and reduced class-switch recombination in exonuclease 1-mutant mice
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DOI：
10.1038/ni1031
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发表时间：
2004-02-01
影响因子：
30.5
通讯作者：
Scharff, MD
中科院分区：
文献类型：
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作者：
Bardwell, PD;Woo, CJ;Scharff, MD
保护性抗体的产生需要免疫球蛋白基因的体细胞高频突变（SHM）和类别转换重组（CSR）。在此我们表明，参与DNA错配修复（MMR）的核酸外切酶1（Exo1）突变的小鼠，其类别转换重组减少，并且体细胞高频突变的特征变化与先前在MMR蛋白Msh2突变的小鼠中观察到的相似。因此，Exo1是首个被证明参与体细胞高频突变和类别转换重组的核酸外切酶。Exo1（-/-）小鼠的表型以及Exo1和Mlh1与可变区突变存在物理关联这一发现，支持了Exo1和错配修复直接参与体细胞高频突变和类别转换重组这一观点。
The generation of protective antibodies requires somatic hypermutation (SHM) and class-switch recombination (CSR) of immunoglobulin genes. Here we show that mice mutant for exonuclease 1 (Exo1), which participates in DNA mismatch repair (MMR), have decreased CSR and changes in the characteristics of SHM similar to those previously observed in mice mutant for the MMR protein Msh2. Exo1 is thus the first exonuclease shown to be involved in SHM and CSR. The phenotype of Exo1(-/-) mice and the finding that Exo1 and Mlh1 are physically associated with mutating variable regions support the idea that Exo1 and MMR participate directly in SHM and CSR.