Stavnezer Janet, Schrader Carol E
Department of Molecular Genetics and Microbiology, Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655-0122, USA.
Trends Genet. 2006 Jan;22(1):23-8. doi: 10.1016/j.tig.2005.11.002. Epub 2005 Nov 23.
Mismatch repair (MMR) proteins are important for antibody class-switch recombination (CSR), but their roles are unknown. We propose a model for the function of MMR in CSR in which MMR proteins convert single-strand nicks instigated by activation-induced cytidine deaminase (AID) into the double-strand breaks (DSBs) that are required for CSR. This model does not invoke any novel functions for MMR but simply posits that, owing to numerous single-strand nicks in the switch (S) regions of both DNA strands, when MMR proteins are recruited by U:G mismatches, they excise one strand of DNA and soon reach a nick on the opposite strand. This halts excision activity and creates a DSB. This model explains why B cells that lack either S mu and MSH2 or UNG and MSH2 cannot undergo CSR.
错配修复（MMR）蛋白对抗体类别转换重组（CSR）很重要，但其作用尚不清楚。我们提出了一个MMR在CSR中功能的模型，其中MMR蛋白将由激活诱导的胞苷脱氨酶（AID）引发的单链切口转化为CSR所需的双链断裂（DSB）。该模型并未赋予MMR任何新功能，只是假定由于两条DNA链的转换（S）区域存在大量单链切口，当MMR蛋白被U:G错配招募时，它们会切除一条DNA链，并很快在相反链上遇到一个切口。这会停止切除活性并产生一个DSB。该模型解释了为什么缺乏Sμ和MSH2或UNG和MSH2的B细胞不能进行CSR。
