AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations.
AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations.
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DOI：
10.1016/j.cell.2008.09.062
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发表时间：
2008-12-12
期刊：
影响因子：
64.5
通讯作者：
Nussenzweig MC
中科院分区：
文献类型：
--
作者：
Robbiani DF;Bothmer A;Callen E;Reina-San-Martin B;Dorsett Y;Difilippantonio S;Bolland DJ;Chen HT;Corcoran AE;Nussenzweig A;Nussenzweig MC
染色体易位需要在异源染色体上形成成对的双链DNA断裂（DSB）。其中一个最好的特点致癌易位并列c-myc和免疫球蛋白重链基因座（IgH），并发现在伯基特淋巴瘤在人类和浆细胞瘤在小鼠。IgH中的DNA断裂导致c-myc/IgH易位，这是在抗体类别转换重组或体细胞超突变期间通过激活诱导的胞苷脱氨酶（AID）产生的。然而，c-myc的DNA断裂来源尚不清楚。在这里，我们提供的证据c-myc启动子区所需的靶向艾滋病介导的DNA损伤，产生DSB的c-myc，导致c-myc/IgH易位在初级B淋巴细胞。因此，除了在抗体基因中产生体细胞突变和DNA断裂外，AID还负责癌基因中的DNA损伤，这是癌基因易位所必需的。
Chromosomal translocation requires formation of paired double strand DNA breaks (DSBs) on heterologous chromosomes. One of the most well characterized oncogenic translocations juxtaposes c-myc and the immunoglobulin heavy chain locus (IgH) and is found in Burkitt’s lymphomas in humans and plasmacytomas in mice. DNA breaks in IgH leading to c-myc/IgH translocations are created by activation induced cytidine deaminase (AID) during antibody class switch recombination or somatic hypermutation. However, the source of DNA breaks at c-myc is not known. Here we provide evidence for the c-myc promoter region being required in targeting AID-mediated DNA damage to produce DSBs in c-myc that lead to c-myc/IgH translocations in primary B lymphocytes. Thus, in addition to producing somatic mutations and DNA breaks in antibody genes, AID is also responsible for the DNA lesions in oncogenes that are required for their translocation.
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