VDJ recombination: Artemis and its in vivo role in hairpin opening.
VDJ recombination: Artemis and its in vivo role in hairpin opening.
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VDJ重组：Artemis及其在发夹开口中的体内作用。
DOI：
10.1084/jem.20022210
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发表时间：
2003-03-03
影响因子：
15.3
通讯作者：
Cortes, P
中科院分区：
文献类型：
--
作者：
Mansilla-Soto, J;Cortes, P
Artemis is the newest player in VDJ recombination and double strand break repair. First identified in radiationsensitive and immune-deficient patients, it was recently shown to interact with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and have nuclease activity, becoming the most popular candidate for the opening of hairpin coding ends. Reports presented in this issue (1) and in the December issue of Molecular Cell (2) address the role of Artemis in vivo by studying the effect of its deletion on the generation of intermediates and products of VDJ recombination in mouse ES cells, MEFs, and thymocytes. In all three systems analyzed, a defect in coding joint formation was observed, which was highly dependent on the cellular background and included inefficient and partially defective opening of hairpin coding ends. In addition, Artemis-deficient ES cells and Artemis-deficient MEFs show spontaneous chromosomal abnormalities, including telomere fusions, indicating that Artemis is also required for maintenance of genomic stability. This commentary will focus on the results regarding the role of Artemis in VDJ recombination. VDJ recombination, also known as antigen receptor gene rearrangement, is the process that assembles the variable domain of immunoglobulin and TCR genes. The hallmark of this reaction is the production of a large repertoire of antigen receptors with different specificities, a characteristic that is essential to the normal functioning of the immune system.VDJ recombination is directed to the immunoglobulin and TCR loci by highly conserved recombination signal sequences (RSSs) comprised of a heptamer and a nonamer motif with an intervening 12-or 23-bp spacer. Efficient recombination in vivo occurs almost exclusively between RSSs with different spacers, which is referred to as the 12/23 rule (3). Several proteins that mediate VDJ recombination in vivo have been identified (4). The lymphoid-specific components of the recombination machinery are RAG-1, RAG-2, and terminal deoxynucleotidyl transferase (TdT). RAG-1 and RAG-2 together constitute the recombinase. TdT, although not essential for catalysis, plays an important
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影响因子：
16
作者：
Besmer, E;Mansilla-Soto, J;Cortes, P
通讯作者：
Cortes, P
影响因子：
10.5
作者：
Tsai, CL;Drejer, AH;Schatz, DG
通讯作者：
Schatz, DG
缺陷的DNA修复和增加的缺乏小鼠细胞中的基因组不稳定性。
影响因子：
15.3
作者：
Rooney, S;Alt, FW;Lombard, D;Whitlow, S;Eckersdorff, M;Fleming, J;Fugmann, S;Ferguson, DO;Schatz, DG;Sekiguchi, J
通讯作者：
Sekiguchi, J
影响因子：
56.9
作者：
Chen, HT;Bhandoola, A;Nussenzweig, A
通讯作者：
Nussenzweig, A
影响因子：
15.3
作者：
Nicolas, N;Moshous, D;de Villartay, JP
通讯作者：
de Villartay, JP