Werner syndrome exonuclease catalyzes structure-dependent degradation of DNA.
Werner syndrome exonuclease catalyzes structure-dependent degradation of DNA.
复制标题
沃纳综合征核酸外切酶催化结构依赖性 DNA 降解。
DOI：
10.1093/nar/28.17.3260
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发表时间：
2000
影响因子：
14.9
通讯作者：
Loeb,LA
中科院分区：
文献类型：
--
作者：
Shen,JC;Loeb,LA
Werner综合征（WS）是一种常染色体隐性遗传疾病，其特征是许多衰老特征的早发性、不寻常的癌症谱和基因组不稳定性。WS蛋白（WRN）具有3′→5′ DNA解旋酶和相关的ATP酶活性，以及3′→5′ DNA核酸外切酶活性。目前，WRN是广泛分布的RecQ DNA解旋酶家族中唯一一个具有外切核酸酶活性的成员。目前尚不清楚WRN的核酸外切酶或解旋酶/ATP酶活性的缺乏，或它们全部的缺乏，是否是WS表型的各种元素的原因。WRN外切核酸酶与大肠杆菌RNaseD（一种tRNA加工酶）具有有限的同源性。我们在这里表明，WRN优先降解含有交替二级结构的合成DNA底物，提示RNaseD的核酸外切作用模式。我们提出的证据表明，WRN与DNA的结构依赖性结合需要ATP结合，而DNA降解需要ATP水解。显然，核酸外切酶和ATP酶协同作用以催化结构依赖性DNA降解。我们建议WRN蛋白作为一种DNA加工酶，通过核酸外切酶和解旋酶的活性来解析异常的DNA结构。
Werner syndrome (WS) is an autosomal recessive disease characterized by early onset of many features of aging, by an unusual spectrum of cancers, and by genomic instability. The WS protein (WRN) possesses 3′→5′ DNA helicase and associated ATPase activities, as well as 3′→5′ DNA exonuclease activity. Currently, WRN is the only member of the widely distributed RecQ DNA helicase family with documented exonuclease activity. It is not known whether deficiency of the exonuclease or helicase/ATPase activities of WRN, or all of them, is responsible for various elements of the WS phenotype. WRN exonuclease has limited homology toEscherichia coliRNaseD, a tRNA processing enzyme. We show here that WRN preferentially degrades synthetic DNA substrates containing alternate secondary structures, with an exonucleolytic mode of action suggestive of RNaseD. We present evidence that structure-dependent binding of WRN to DNA requires ATP binding, while DNA degradation requires ATP hydrolysis. Apparently, the exonuclease and ATPase act in concert to catalyze structure-dependent DNA degradation. We propose that WRN protein functions as a DNA processing enzyme in resolving aberrant DNA structures via both exonuclease and helicase activities.