A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA.
A functional interaction of Ku with Werner exonuclease facilitates digestion of damaged DNA.
复制标题
Ku 与 Werner 核酸外切酶的功能性相互作用促进受损 DNA 的消化。
DOI：
10.1093/nar/29.9.1926
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发表时间：
2001
影响因子：
14.9
通讯作者：
Bohr,VA
中科院分区：
文献类型：
--
作者：
Orren,DK;Machwe,A;Karmakar,P;Piotrowski,J;Cooper,MP;Bohr,VA
沃纳综合征（WS）是一种早衰症，患者看起来比实际年龄老得多。WS中有缺陷的单基因编码一种蛋白（WRN），该蛋白具有atp酶、解旋酶和3 ‘→5 ’外切酶活性。我们的实验室最近发现了WRN和Ku异源二聚体复合物之间的物理和功能相互作用，该相互作用在双链断裂修复和V(D)J重组中起作用。重要的是，Ku特异性地刺激WRN的外切酶活性。我们现在报道Ku使Werner外切酶能够通过含有8-氧腺嘌呤和8-氧鸟嘌呤修饰的DNA区域进行消化，这些病变先前已被证明可以单独阻断WRN的外切酶活性。这些结果表明，Ku显著改变了WRN的外切酶功能，并表明这两种蛋白在DNA损伤加工途径中同时起作用。为了支持这一观点，我们还观察到WRN和Ku的共定位，特别是在DNA损伤处理后。
Werner syndrome(WS)is a premature aging disorder where the affected individuals appear much older than their chronological age. The single gene that is defective in WS encodes a protein (WRN) that has ATPase, helicase and 3′→5′ exonuclease activities. Our laboratory has recently uncovered a physical and functional interaction between WRN and the Ku heterodimer complex that functions in double-strand break repair and V(D)J recombination. Importantly, Ku specifically stimulates the exonuclease activity of WRN. We now report that Ku enables the Werner exonuclease to digest through regions of DNA containing 8-oxoadenine and 8-oxoguanine modifications, lesions that have previously been shown to block the exonuclease activity of WRN alone. These results indicate that Ku significantly alters the exonuclease function of WRN and suggest that the two proteins function concomitantly in a DNA damage processing pathway. In support of this notion we also observed co-localization of WRN and Ku, particularly after DNA damaging treatments.