AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation
AID binds to transcription-induced structures in c-MYC that map to regions associated with translocation and hypermutation
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DOI：
10.1038/sj.onc.1208746
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发表时间：
2005-09-01
期刊：
影响因子：
8
通讯作者：
Maizels, N
中科院分区：
文献类型：
--
作者：
Duquette, ML;Pham, P;Maizels, N
在B细胞淋巴瘤中，c-MYC的易位和异常超突变是常见的。激活诱导的胞苷脱氨酶（AID）通过转录基因的靶向脱氨作用启动B细胞中的开关重组和体细胞超变。我们发现，免疫球蛋白S区和c-MYC的转录导致形成类似的DNA结构，“G-环”，其中包含一个cotranscriptional RNA：富含C链的DNA杂交和单链区域和G4 DNA上的G-丰富的链。AID特异性结合转录的S区和c-MYC内的G环，并且c-MYC中的G环映射到与B细胞淋巴瘤中的易位断点和异常超突变相关的区域。因此，AID异常靶向c-MYC转录后形成的DNA结构可能导致B细胞恶性肿瘤中c-MYC的遗传不稳定性。
Translocation and aberrant hypermutation of c-MYC are common in B-cell lymphomas. Activation-induced Cytidine Deaminase (AID) initiates switch recombination and somatic hypermutation in B cells by targeted deamination of transcribed genes. We show that transcription of the immunoglobulin S regions and c-MYC results in formation of similar DNA structures, 'G-loops', which contain a cotranscriptional RNA: DNA hybrid on the C-rich strand and single-stranded regions and G4 DNA on the G-rich strand. AID binds specifically to G-loops within transcribed S regions and c-MYC, and G-loops in c-MYC map to the regions associated with translocation breakpoints and aberrant hypermutation in B-cell lymphomas. Aberrant targeting of AID to DNA structures formed upon c-MYC transcription may therefore contribute to the genetic instability of c-MYC in B-cell malignancies.