The Sμ tandem repeat region is critical for Ig isotype switching in the absence of Msh2
The Sμ tandem repeat region is critical for Ig isotype switching in the absence of Msh2
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DOI：
10.1016/s1074-7613(03)00262-0
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发表时间：
2003-10-01
期刊：
影响因子：
32.4
通讯作者：
Selsing, E
中科院分区：
文献类型：
--
作者：
Min, IM;Schrader, CE;Selsing, E
Msh2蛋白或Smu串联重复序列（SmuTR）的缺失，各自都会使小鼠的同种型转换降低约2到3倍。我们发现，Msh2和SmuTR两者均缺失的小鼠的转换几乎完全消失。我们提出，SmuTR提供了紧密间隔的切割位点，这些位点可不依赖Msh2进行转换重组，而SmuTR侧翼序列的切割则需要Msh2的加工才能进行重组连接。我们还发现，Smu序列的改变会改变Sγ序列内转换连接的焦点，这表明转换区域的序列在转换重组连接的选择中共同起作用。这些发现有助于解释在具有转换能力的物种中与重链恒定基因相关的串联重复转换区域的保守性。
Deficiencies of the Msh2 protein or the Smu tandem repeat (SmuTR) sequences each reduce isotype switching in mice by about 2- to 3-fold. We find that switching in mice deficient for both Msh2 and SmuTR is nearly ablated. We propose that the SmuTR provides closely spaced cleavage sites that can undergo switch recombination independent of Msh2, whereas cleavages in sequences flanking the SmuTR require Msh2 processing to allow recombinational joining. We also find that changes in Smu sequences alter the focus of switch junctions within Sgamma sequences, indicating that sequences of switch regions act together in the choice of switch recombination junctions. These findings help to explain the conservation of tandemly repeated switch regions associated with heavy chain constant genes in species capable of switching.