ATM 和 DNA-PKcs 在 V(D)J 重组过程中的独特和冗余功能。
Unique and redundant functions of ATM and DNA-PKcs during V(D)J recombination.
机构信息
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
出版信息
Cell Cycle. 2011 Jun 15;10(12):1928-35. doi: 10.4161/cc.10.12.16011.
Abstract
Lymphocyte antigen receptor genes are assembled through the process of V(D)J recombination, during which pairwise DNA cleavage of gene segments results in the formation of four DNA ends that are resolved into a coding joint and a signal joint. The joining of these DNA ends occurs in G1-phase lymphocytes and is mediated by the non-homologous end-joining (NHEJ) pathway of DNA double-strand break (DSB) repair. The ataxia telangiectasia mutated (ATM) and the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), two related kinases, both function in the repair of DNA breaks generated during antigen receptor gene assembly. Although these proteins have unique functions during coding joint formation, their activities in signal joint formation, if any, have been less clear. However, two recent studies demonstrated that ATM and DNA-PKcs have overlapping activities important for signal joint formation. Here, we discuss the unique and shared activities of the ATM and DNA-PKcs kinases during V(D)J recombination, a process that is essential for lymphocyte development and the diversification of antigen receptors.
摘要
淋巴细胞抗原受体基因通过 V(D)J 重组过程进行组装，在此过程中基因片段的两两 DNA 切割导致四个 DNA 末端的形成，这些末端被解析为编码连接和信号连接。这些 DNA 末端的连接发生在 G1 期淋巴细胞中，并由 DNA 双链断裂 (DSB) 修复的非同源末端连接 (NHEJ) 途径介导。共济失调毛细血管扩张突变 (ATM) 和 DNA 依赖性蛋白激酶催化亚基 (DNA-PKcs) 是两种相关的激酶，它们都参与了抗原受体基因组装过程中产生的 DNA 断裂的修复。尽管这些蛋白在编码连接形成过程中具有独特的功能，但它们在信号连接形成中的活性（如果有的话）则不太清楚。然而，最近的两项研究表明，ATM 和 DNA-PKcs 在信号连接形成中具有重叠的活性，这对于信号连接形成是至关重要的。在这里，我们讨论了 ATM 和 DNA-PKcs 激酶在 V(D)J 重组过程中的独特和共享活动，该过程对于淋巴细胞发育和抗原受体的多样化是必不可少的。
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Ataxia telangiectasia mutated (Atm) and DNA-PKcs kinases have overlapping activities during chromosomal signal joint formation.共济失调毛细血管扩张症突变基因 (Atm) 和 DNA 依赖性蛋白激酶催化亚基 (DNA-PKcs) 在染色体信号连接形成过程中有重叠的活性。
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Histone H2AX stabilizes broken DNA strands to suppress chromosome breaks and translocations during V(D)J recombination.组蛋白H2AX可稳定断裂的DNA链，以抑制V(D)J重组过程中的染色体断裂和易位。
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