The activation-induced cytidine deaminase (AID) efficiently targets DNA in nucleosomes but only during transcription.
The activation-induced cytidine deaminase (AID) efficiently targets DNA in nucleosomes but only during transcription.
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DOI：
10.1084/jem.20082678
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发表时间：
2009-05-11
期刊：
影响因子：
--
通讯作者：
Storb U
中科院分区：
文献类型：
--
作者：
Shen HM;Poirier MG;Allen MJ;North J;Lal R;Widom J;Storb U
激活诱导型胞苷脱氨酶(AID)启动体细胞超突变、类切换重组和免疫球蛋白基因的基因转换。在体外，AID被证明在转录时以单链DNA、松弛双链DNA或超螺旋DNA为靶标。为了更好地模拟体内的情况，我们将核小体定位序列MP2的两个副本引入超螺旋AID靶质粒中，以确定在没有或存在转录的情况下，定位的核小体(在氨苄西林耐药基因附近)胞苷脱氨基发生在哪里。我们发现，在没有转录的情况下，核小体可以阻止AID导致的胞苷脱氨。然而，通过转录，AID很容易在两条DNA链上的核小体中获得DNA。实验还表明，AID靶向任何DNA分子都是限制步骤，并支持这样的结论，即一旦靶向DNA，AID就会在裸露的DNA和转录的核小体内的DNA中连续发挥作用。
The activation-induced cytidine deaminase (AID) initiates somatic hypermutation, class-switch recombination, and gene conversion of immunoglobulin genes. In vitro, AID has been shown to target single-stranded DNA, relaxed double-stranded DNA, when transcribed, or supercoiled DNA. To simulate the in vivo situation more closely, we have introduced two copies of a nucleosome positioning sequence, MP2, into a supercoiled AID target plasmid to determine where around the positioned nucleosomes (in the vicinity of an ampicillin resistance gene) cytidine deaminations occur in the absence or presence of transcription. We found that without transcription nucleosomes prevented cytidine deamination by AID. However, with transcription AID readily accessed DNA in nucleosomes on both DNA strands. The experiments also showed that AID targeting any DNA molecule was the limiting step, and they support the conclusion that once targeted to DNA, AID acts processively in naked DNA and DNA organized within transcribed nucleosomes.
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