Activation-induced cytosine deaminase (AID) is actively exported out of the nucleus but retained by the induction of DNA breaks
Activation-induced cytosine deaminase (AID) is actively exported out of the nucleus but retained by the induction of DNA breaks
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DOI：
10.1074/jbc.m403503200
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发表时间：
2004-06-18
影响因子：
4.8
通讯作者：
Diaz, M
中科院分区：
文献类型：
--
作者：
Brar, SS;Watson, M;Diaz, M
激活诱导的胞嘧啶脱氨酶（AID）是一种对免疫球蛋白超突变、类别转换重组和基因转换至关重要的胞嘧啶脱氨酶。在高突变B细胞的情况下，AID使免疫球蛋白基因DNA中的胞嘧啶脱氨基，导致可变区中突变的积累。然而，当AID异位表达时，它是G：C碱基对的广义增变子。因此，我们询问AID是否可以通过活跃的核出口制度进行部分监管。我们发现，在AID的C末端的高度保守的核输出信号的去除引起AID在细胞核中的积累。然而，一个假定的核定位信号在N端似乎没有功能。最后，我们发现，诱导DNA断裂的药物导致AID保留在细胞核中，这表明DNA断裂或由此引发的修复补丁是AID结合的底物。
Activation-induced cytosine deaminase (AID) is a cytosine deaminase that is critical to immunoglobulin hypermutation, class switch recombination, and gene conversion. In the context of hypermutating B cells, AID deaminates cytosine in the DNA of immunoglobulin genes, leading to the accumulation of mutations in the variable regions. However, when AID is expressed ectopically, it is a generalized mutator of G: C base pairs. Therefore, we asked whether AID may be partially regulated by an active system of nuclear export. We found that removal of a highly conserved nuclear export signal in the C terminus of AID causes accumulation of AID in the nucleus. However, a putative nuclear localization signal in the N terminus does not appear to be functional. Finally, we found that agents that induce DNA breaks caused retention of AID in the nucleus, suggesting that DNA breaks or the repair patches initiated as a result are a substrate for AID binding.