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首页> 外文期刊>Cell cycle >B-cell differentiation stimulated by physiologic DNA double strand breaks.
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B-cell differentiation stimulated by physiologic DNA double strand breaks.

机译:生理DNA双链断裂刺激B细胞分化。

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摘要

DNA double strand breaks (DSBs) induced by stage-specific endonucleases are required for the assembly and diversification of B-cell antigen receptor (BCR) genes in developing vertebrate B lymphocytes. BCR genes encode for antibodies that contain immunoglobulin (Ig) heavy (H) and light (L) chains and are assembled by the somatic recombination of variable (V), diversity (D) and joining (J) gene segments. In the bone marrow, the recombinase activating gene (RAG) endo-nuclease generates DNA DSBs in developing B cells at the border of two Ig gene segments and their flanking recombination signal sequences.1 RAG DSBs activate a DNA damage response (DDR) program orchestrated by damage-sensing kinases, such as ATM, which phosphorylates hundreds of proteins that participate in DNA repair, tumor suppression and cell cycle regulation.
机译:在发育中的脊椎动物B淋巴细胞中,B细胞抗原受体(BCR)基因的组装和多样化需要阶段特异性核酸内切酶诱导的DNA双链断裂(DSB)。 BCR基因编码包含免疫球蛋白(Ig)重链(H)和轻链(L)的抗体,并通过可变(V),多样性(D)和连接(J)基因区段的体细胞重组组装而成。在骨髓中,重组酶激活基因(RAG)内切酶在两个Ig基因片段和其侧翼重组信号序列边界的发育中B细胞中产生DNADSB。1RAG DSB激活精心设计的DNA损伤反应(DDR)程序。通过损伤感应激酶(例如ATM)使参与DNA修复,肿瘤抑制和细胞周期调节的数百种蛋白质磷酸化。

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