RNaseH2 mutants that cause Aicardi-Goutieres syndrome are active nucleases.
RNaseH2 mutants that cause Aicardi-Goutieres syndrome are active nucleases.
复制标题
DOI：
10.1007/s00109-008-0422-3
复制
发表时间：
2009-01
影响因子：
4.7
通讯作者：
Hollis, Thomas
中科院分区：
文献类型：
--
作者：
Perrino, Fred W.;Harvey, Scott;Shaban, Nadine M.;Hollis, Thomas
在Aicardi-Goutieres综合征(AGS)患者中发现了编码RNaseH2和TREX1核酸酶的基因突变。为了确定AGS RNaseH2突变是否导致核酸酶活性丧失，我们制备了人野生型RNaseH2和四个突变复合体，它们构成了AGS患者中发现的大多数突变，并对核糖核酸酶H活性进行了测试。突变的RNaseH2复合体的异三聚体结构是完整的。此外，除了RNaseH2亚基A(Gly37Ser)突变外，突变复合体的核糖核酸酶H活性与野生型酶没有区别，这表明核酸酶特异性发生了一些变化。这些数据表明，AGS中RNaseH2功能障碍的机制不能简单地用核糖核酸酶H活性的丧失来解释，而是一种更复杂的机制，可能是通过与尚未确定的核酸或蛋白质伙伴的相互作用而调节的。
Mutations in the genes encoding the RNaseH2 and TREX1 nucleases have been identified in patients with Aicardi-Goutieres syndrome (AGS). To determine if the AGS RNaseH2 mutations result in the loss of nuclease activity, the human wild-type RNaseH2 and four mutant complexes that constitute the majority of mutations identified in AGS patients have been prepared and tested for ribonuclease H activity. The heterotrimeric structures of the mutant RNaseH2 complexes are intact. Furthermore, the ribonuclease H activities of the mutant complexes are indistinguishable from the wild-type enzyme with the exception of the RNaseH2 subunit A (Gly37Ser) mutant, which exhibits some evidence of altered nuclease specificity. These data indicate that the mechanism of RNaseH2 dysfunction in AGS cannot be simply explained by loss of ribonuclease H activity and points to a more complex mechanism perhaps mediated through altered interactions with as yet identified nucleic acids or protein partners.
登录
查看更多内容
影响因子：
64.5
作者：
Stetson DB;Ko JS;Heidmann T;Medzhitov R
通讯作者：
Medzhitov R
影响因子：
9.8
作者：
Rice, Gillian;Newman, William G.;Crow, Yanick J.
通讯作者：
Crow, Yanick J.
影响因子：
4.3
作者：
Kavanagh, David;Spitzer, Dirk;Atkinson, John P.
通讯作者：
Atkinson, John P.
影响因子：
4.7
作者：
Lee-Kirsch, Min Ae;Chowdhury, Dipanjan;Hubner, Norbert
通讯作者：
Hubner, Norbert
影响因子：
30.8
作者：
Crow, Yanick J.;Leitch, Andrea;Jackson, Andrew P.
通讯作者：
Jackson, Andrew P.