Duquette Michelle L, Pham Phuong, Goodman Myron F, Maizels Nancy
Department of Biochemistry, University of Washington Medical School, Seattle, 98195-7650, USA.
Oncogene. 2005 Sep 1;24(38):5791-8. doi: 10.1038/sj.onc.1208746.
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.
c-MYC的易位和异常高突变在B细胞淋巴瘤中很常见。激活诱导的胞苷脱氨酶（AID）通过对转录基因进行靶向脱氨作用，启动B细胞中的类别转换重组和体细胞高突变。我们发现，免疫球蛋白S区和c-MYC的转录会导致形成相似的DNA结构，即“G-环”，其在富含C的链上包含一个共转录的RNA:DNA杂交体、单链区域，在富含G的链上包含G4 DNA。AID特异性结合转录的S区和c-MYC内的G-环，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高突变相关的区域。因此，AID异常靶向c-MYC转录时形成的DNA结构可能导致B细胞恶性肿瘤中c-MYC的遗传不稳定性。
