Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs.
Artemis C-terminal region facilitates V(D)J recombination through its interactions with DNA Ligase IV and DNA-PKcs.
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DOI：
10.1084/jem.20111437
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发表时间：
2012-05-07
期刊：
影响因子：
--
通讯作者：
Cortes P
中科院分区：
文献类型：
--
作者：
Malu S;De Ioannes P;Kozlov M;Greene M;Francis D;Hanna M;Pena J;Escalante CR;Kurosawa A;Erdjument-Bromage H;Tempst P;Adachi N;Vezzoni P;Villa A;Aggarwal AK;Cortes P
Artemis与DNA连接酶IV和DNA- pkcs的相互作用是有效编码关节形成所必需的。Artemis是一种核酸内切酶，在V(D)J重组过程中打开编码发夹末端，在辐射后细胞存活中起关键作用。Artemis的c端区域在V(D)J重组中的直接作用尚未明确，尽管该区域缺失的患者存在免疫缺陷和淋巴瘤发展。本文中，我们报道了Artemis c端区域直接与连接酶IV的DNA结合域相互作用，而连接酶IV在DNA修复和V(D)J重组中起着重要作用。Artemis - ligase IV相互作用是特异性的，并且独立于DNA和DNA-蛋白激酶催化亚基（DNA- pkcs）的存在而发生，DNA-蛋白激酶催化亚基是另一种已知与Artemis c -末端区域相互作用的蛋白质。在Artemis中，破坏其与连接酶IV或DNA-PKcs相互作用的点突变会减少V(D)J重组，而影响与连接酶IV和DNA-PKcs相互作用的Artemis突变对编码关节的形成具有累加性的有害影响。信号关节形成不受影响。我们的数据显示，Artemis的c端区域通过与连接酶IV和DNA-PKcs的相互作用影响V(D)J重组。
Interactions of Artemis with DNA Ligase IV and DNA-PKcs are required for efficient coding joint formation. Artemis is an endonuclease that opens coding hairpin ends during V(D)J recombination and has critical roles in postirradiation cell survival. A direct role for the C-terminal region of Artemis in V(D)J recombination has not been defined, despite the presence of immunodeficiency and lymphoma development in patients with deletions in this region. Here, we report that the Artemis C-terminal region directly interacts with the DNA-binding domain of Ligase IV, a DNA Ligase which plays essential roles in DNA repair and V(D)J recombination. The Artemis–Ligase IV interaction is specific and occurs independently of the presence of DNA and DNA–protein kinase catalytic subunit (DNA-PKcs), another protein known to interact with the Artemis C-terminal region. Point mutations in Artemis that disrupt its interaction with Ligase IV or DNA-PKcs reduce V(D)J recombination, and Artemis mutations that affect interactions with Ligase IV and DNA-PKcs show additive detrimental effects on coding joint formation. Signal joint formation remains unaffected. Our data reveal that the C-terminal region of Artemis influences V(D)J recombination through its interaction with both Ligase IV and DNA-PKcs.
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