Activation-induced cytidine deaminase (AID) initiates immunoglobulin (Ig) class switch recombination (CSR), somatic hypermutation (SHM), and gene conversion by converting DNA cytosines to uracils at specific genomic regions. In this study, we examined AID footprints across the entire length of an engineered switch region in cells ablated for uracil repair. We found that AID deamination occurs predominantly at WRC hot spots (where W is A or T and R is A or G) and that the deamination frequency remains constant across the entire switch region. Importantly, we analyzed monoallelic AID deamination footprints on both DNA strands occurring within a single cell cycle. We found that AID generates few and mostly isolated uracils in the switch region, although processive AID deaminations are evident in some molecules. The frequency of molecules containing deamination on both DNA strands at the acceptor switch region correlates with the class switch efficiency, raising the possibility that the minimal requirement for DNA double-strand break (DSB) formation is as low as even one AID deamination event on both DNA strands.

中文翻译：

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免疫球蛋白类开关重组是由开关区域的罕见胞嘧啶脱氨事件引发的。

激活诱导的胞苷脱氨酶（AID）通过将DNA胞嘧啶转化为特定基因组区域的尿嘧啶来启动免疫球蛋白（Ig）类转换重组（CSR），体细胞超突变（SHM）和基因转换。在这项研究中，我们检查了在为尿嘧啶修复而消融的细胞中工程开关区域整个长度上的AID足迹。我们发现，AID脱氨主要发生在WRC热点（其中W为A或T，R为A或G），并且脱氨频率在整个开关区域内保持恒定。重要的是，我们分析了单个细胞周期内两条DNA链上的单等位基因AID脱氨足迹。我们发现，尽管在某些分子中进行性的AID脱氨基作用明显，但AID在转换区几乎不产生尿嘧啶，而且大多数是孤立的尿嘧啶。