A conserved and species-specific functional interaction between the Werner syndrome-like exonuclease atWEX and the Ku heterodimer in Arabidopsis.
A conserved and species-specific functional interaction between the Werner syndrome-like exonuclease atWEX and the Ku heterodimer in Arabidopsis.
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拟南芥中沃纳综合征样核酸外切酶 atWEX 和 Ku 异二聚体之间保守且物种特异性的功能相互作用。
DOI：
10.1093/nar/gki984
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发表时间：
2005
影响因子：
14.9
通讯作者：
Comai,Lucio
中科院分区：
文献类型：
--
作者：
Li,Baomin;Conway,Nathan;Navarro,Sonia;Comai,Luca;Comai,Lucio
沃纳综合征与DNA解旋酶RecQ 3 [又名智人（hs）WRN]的突变相关。hsWRN的功能是未知的，虽然生化研究表明，在DNA末端的稳定性和修复的作用。与其他RecQ家族成员不同，hsWRN具有一个具有核酸外切酶活性的N-末端结构域，其通过与Ku异源二聚体的相互作用而被刺激。虽然这种相互作用很有趣，但我们不知道它对hsWRN功能是否重要。虽然苍蝇、蠕虫、真菌和植物不具有具有内在核酸外切酶活性的RecQ样（RQL）解旋酶，但它们具有具有与hsWRN核酸外切酶同源的结构域的蛋白质。拟南芥（Arabidopsis thaliana，at）基因组编码多个RQL和一个与WRN外切核酸酶结构域同源的蛋白质atWEX（Werner-like Exonuclease，WEX）。在这里，我们表明atWEX具有类似于hsWRN的性质。atWEX结合到atKu并被atKu刺激。有趣的是，Ku的刺激是物种特异性的，ashsKu不刺激WEX核酸外切酶活性。同样，atKu不能增强hsWRN的核酸外切酶活性。因此，尽管在结构组织的差异，WRN样核酸外切酶和Ku之间的功能相互作用已通过物种的进化辐射保存，强调这种相互作用在细胞功能的重要性。
Werner syndrome is associated with mutations in the DNA helicase RecQ3 [a.k.a.Homo sapiens(hs)WRN]. The function ofhsWRN is unknown although biochemical studies suggest a role in DNA ends stability and repair. Unlike other RecQ family members,hsWRN possesses an N-terminal domain with exonuclease activity, which is stimulated by interaction with the Ku heterodimer. While this interaction is intriguing, we do not know whether it is important forhsWRN function. Although flies, worms, fungi and plants do not have RecQ-like (RQL) helicases with an intrinsic exonuclease activity, they possess proteins having domains homologous to thehsWRN exonuclease. The genome ofArabidopsis thaliana(at) encodes multiple RQL and a single protein with homology to the WRN exonuclease domain,atWEX (Werner-like Exonuclease). Here we show thatatWEX has properties that are similar tohsWRN.atWEX binds to and is stimulated byatKu. Interestingly, stimulation by Ku is species-specific, ashsKu does not stimulateatWEX exonuclease activity. Likewise,atKu fails to enhance the exonuclease activity ofhsWRN. Thus, in spite of the differences in structural organization, the functional interaction between WRN-like exonucleases and Ku has been preserved through evolutionary radiation of species, emphasizing the importance of this interaction in cell function.