ATM 防止了淋巴细胞中染色体断裂的持续和传播
Elsa Callén1, Mila Jankovic, Simone Difilippantonio
1Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA.
Cell
|June 30, 2007
概括
淋巴细胞中阿塔克西亚-泰朗吉克塔西亚突变 (ATM) 激酶缺乏导致V(D) J重组期间DNA修复失败导致端粒被删除的末端. 恢复ATM功能可以消除这些不稳定的染色体,保持基因组的稳定性.
科学领域:
- 遗传学 是一个遗传学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 双链DNA断裂 (DSBs) 触发了阿塔克西亚-特朗吉克塔西亚突变 (ATM) 激酶信号传递.
- 在抑制非合法DSB连接和激活细胞循环检查点方面,ATM激酶活性至关重要.
研究的目的:
- 研究ATM缺陷对淋巴细胞基因组稳定性的后果.
- 确定ATM在防止V(D) J重组过程中DNA修复错误的传播中的作用.
主要方法:
- 端粒被删除的染色体的分析以ATM缺乏的淋巴细胞结束.
- 这些异常染色体的体内和体外稳定性评估.
- 评估ATM恢复对终端删除染色体的细胞的影响.
主要成果:
- 很大一部分成熟的ATM缺乏的淋巴细胞中存在着由于V(D) J重组末端连接有缺陷而导致的端粒被删除的末端.
- 这些RAG-1/2内核酶依赖的删除染色体在淋巴细胞中长时间保持稳定.
- 在缺乏ATM功能的淋巴细胞中恢复ATM激酶活性可以降低这些终端删除染色体的流行率.
结论:
- 淋巴细胞的基因组稳定性需要精确的DNA末端连接和一个检查点,以防止持久的DSBs.
- 这个检查点的失败允许V(D) J重组生成的DNA末端参与转位,以后发生染色体损伤.
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