High levels of AID cause strand bias of mutations at A versus T in Burkitt's lymphoma cells
High levels of AID cause strand bias of mutations at A versus T in Burkitt's lymphoma cells
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高水平的 AID 会导致伯基特淋巴瘤细胞中 A 与 T 突变的链偏倚
DOI：
10.1016/j.molimm.2013.01.005
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
J.-Y.
中科院分区：
文献类型：
--
作者：
Kano;C. and Wang;J.-Y.
生发中心（GC） B细胞中Ig基因体细胞超突变发生在C和G的频率大致相同。相比之下，在V基因的非转录链上，a位点的突变相对于T位点的突变增加了2倍，但尚不清楚是什么触发了这种链偏倚。利用一种高效的诱变系统，我们在GC B细胞中概括了Ig基因高突变的特征，我们发现低水平的AID诱导了相似频率的A和T突变。然而，高水平的AID特异性地增加了A的突变，而不是T，导致链偏倚。这些结果解释了为什么A:T突变的链偏性只在高突变的V基因中观察到，而在低突变的开关区或BCL-6基因中没有观察到。高水平的AID也增加了G位点相对于c位点的翻转比例。我们的研究结果发现了a:T突变的链偏倚的线索，并提供了一个体外模型来阐明这个在超突变领域未解之谜。
Ig gene somatic hypermutation in the germinal center (GC) B cells occurs at C and G at roughly the same frequency. In contrast, there is a 2-fold increase of mutations at A relative to T on the non-transcribed strand of the V genes but it is unclear what triggers such strand bias. Using an efficient mutagenesis system that recapitulates characteristic features of Ig gene hypermutation in the GC B cells, we found that low levels of AID induced similar frequency of mutations at A and T. However, high levels of AID specifically increased mutations at A, but not T, leading to strand bias. These results explain why strand bias of A:T mutations is observed only in the highly mutated V genes but not in the less mutated switch region or the BCL-6 gene. High levels of AID also increased the proportion of transversions at G relative to transversions at C. Our results identify a clue to the strand bias of A:T mutations and provide an in vitro model to elucidate this unsolved mystery in the hypermutation field.