Structure and mechanism of the UvrA-UvrB DNA damage sensor
Structure and mechanism of the UvrA-UvrB DNA damage sensor
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DOI：
10.1038/nsmb.2240
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发表时间：
2012-03-01
影响因子：
16.8
通讯作者：
Jeruzalmi, David
中科院分区：
文献类型：
--
作者：
Pakotiprapha, Danaya;Samuels, Martin;Jeruzalmi, David
核苷酸切除修复（NER）被所有生物体用来消除DNA损伤。确定了嗜热脂肪土芽孢杆菌（Geobacillusstearothermophilus）UvrA-UvrB复合物的结构，该复合物是细菌NER中的损伤传感器，并确定了UvrA的一种新结构。我们观察到，UvrA的DNA结合表面，以前发现在一个开放的形状，结合受损的DNA，也存在于一个封闭的凹槽形状兼容的天然DNA。传感器包含两个UvrB分子，它们沿着预测的DNA路径位于UvrA二聚体的两侧，类似于距离病变80埃。我们发现，UvrA的保守的签名域II介导的UvrA，UvrB和DNA之间的联系。此外，在我们的UvrA的新结构中，该结构域采用改变的构象，而相邻的核苷酸结合位点是空的。我们的研究结果提出了意料之外的问题，净入学率，也提出了一个修订后的图片，其早期阶段。
Nucleotide excision repair (NER) is used by all organisms to eliminate DNA lesions. We determined the structure of the Geobacillus stearothermophilus UvrA-UvrB complex, the damage-sensor in bacterial NER and a new structure of UvrA. We observe that the DNA binding surface of UvrA, previously found in an open shape that binds damaged DNA, also exists in a closed groove shape compatible with native DNA only. The sensor contains two UvrB molecules that flank the UvrA dimer along the predicted path for DNA, similar to 80 angstrom from the lesion. We show that the conserved signature domain II of UvrA mediates a nexus of contacts among UvrA, UvrB and DNA. Further, in our new structure of UvrA, this domain adopts an altered conformation while an adjacent nucleotide binding site is vacant. Our findings raise unanticipated questions about NER and also suggest a revised picture of its early stages.