Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex.

Structure-Specific nuclease activities of Artemis and the Artemis: DNA-PKcs complex.
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DOI:
10.1093/nar/gkw456
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发表时间:
2016-06-20
影响因子:
14.9
通讯作者:
Lieber MR
Lieber MR
中科院分区:
生物学2区
文献类型:
--
作者:
Chang HH;Lieber MR

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Artemis是一种脊椎动物核酸酶,具有核酸内切酶和核酸外切酶活性,作用于多种核酸底物。它是非同源DNA末端连接途径(NHEJ)中的主要核酸酶。Artemis不仅对NHEJ中DNA双链断裂(DSB)的修复很重要,而且在打开V(D)J重组过程中形成的DNA发夹中间体方面也是必不可少的。因此,患有Artemis缺陷的人没有T或B淋巴细胞,并被诊断为严重联合免疫缺陷(SCID)。虽然Artemis是唯一能够打开DNA发夹的脊椎动物核酸酶,但它也被发现作用于其他具有共同结构特征的DNA底物。在这里,我们讨论了所有Artemis DNA底物具有的关键结构特征,从而为理解这种结构特异性核酸酶如何识别其DNA靶标提供了基础。
Artemis is a vertebrate nuclease with both endo- and exonuclease activities that acts on a wide range of nucleic acid substrates. It is the main nuclease in the non-homologous DNA end-joining pathway (NHEJ). Not only is Artemis important for the repair of DNA double-strand breaks (DSBs) in NHEJ, it is essential in opening the DNA hairpin intermediates that are formed during V(D)J recombination. Thus, humans with Artemis deficiencies do not have T- or B-lymphocytes and are diagnosed with severe combined immunodeficiency (SCID). While Artemis is the only vertebrate nuclease capable of opening DNA hairpins, it has also been found to act on other DNA substrates that share common structural features. Here, we discuss the key structural features that all Artemis DNA substrates have in common, thus providing a basis for understanding how this structure-specific nuclease recognizes its DNA targets.