Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand
Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand
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DOI：
10.1038/ni920
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发表时间：
2003-05-01
影响因子：
30.5
通讯作者：
Nussenzweig, MC
中科院分区：
文献类型：
--
作者：
Ramiro, AR;Stavropoulos, P;Nussenzweig, MC
体细胞超突变和类别转换重组是改变B淋巴细胞中编码抗体的基因的DNA修饰反应。这两种不同的反应都需要活化诱导的脱氨酶（AID）和转录。在这里，我们表明，在大肠杆菌，在真核细胞中，突变频率是成正比的靶基因的转录。转录增强了非模板DNA链的突变，非模板DNA链在延伸反应中作为单链DNA暴露，但不增强模板DNA链的突变，模板DNA链被E. coli RNA聚合酶。我们的研究结果建立了AID和转录之间的直接联系，并表明转录在促进突变中的作用是为AID提供单链DNA。
Somatic hypermutation and class switch recombination are DNA modification reactions that alter the genes encoding antibodies in B lymphocytes. Both of these distinct reactions require activation-induced deaminase (AID) and transcription. Here we show that in Escherichia coli, as in eukaryotic cells, the mutation frequency is directly proportional to the transcription of target genes. Transcription enhances mutation of the nontemplate DNA strand, which is exposed as single-stranded DNA during the elongation reaction, but not mutation of the template DNA strand, which is protected by E. coli RNA polymerase. Our results establish a direct link between AID and transcription and suggest that the role of transcription in facilitating mutation is to provide AID with access to single-stranded DNA.