Architecture of the human XPC DNA repair and stem cell coactivator complex.
Architecture of the human XPC DNA repair and stem cell coactivator complex.
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人类 XPC DNA 修复和干细胞共激活剂复合物的结构。
DOI：
10.1073/pnas.1520104112
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发表时间：
2015
影响因子：
11.1
通讯作者：
Tjian,Robert
中科院分区：
文献类型：
--
作者：
Zhang,ElisaT;He,Yuan;Grob,Patricia;Fong,YickW;Nogales,Eva;Tjian,Robert
着色性干皮病互补组C（XPC）复合物是一种多功能因子，参与核苷酸切除修复和转录共激活，是NANOG、OCT 4和SOX 2多能性基因调控网络的重要组成部分。在这里，我们提出了由单粒子电子显微镜确定的人类holo-XPC复合物的结构，以揭示一个灵活的，耳状的结构，在DNA结合时发生局部失序。我们还确定了完整的酵母同系物Rad 4全息复合物的结构，以找到与人类复合物相似的整体结构，与它们共享的DNA修复功能一致。这些结构之间的局部差异反映了我们在这里提出的转录能力的一个有趣的系统发育分歧。通过标记和删除定位组成亚基，我们提出了一个模型的关键相互作用界面，揭示了这种差异的结构基础上的功能保护。总之，我们的研究结果建立了一个框架，了解转录和DNA修复之间的相互作用的XPC复合物的结构-功能关系。
The Xeroderma pigmentosum complementation group C (XPC) complex is a versatile factor involved in both nucleotide excision repair and transcriptional coactivation as a critical component of theNANOG,OCT4, andSOX2pluripotency gene regulatory network. Here we present the structure of the human holo-XPC complex determined by single-particle electron microscopy to reveal a flexible, ear-shaped structure that undergoes localized loss of order upon DNA binding. We also determined the structure of the complete yeast homolog Rad4 holo-complex to find a similar overall architecture to the human complex, consistent with their shared DNA repair functions. Localized differences between these structures reflect an intriguing phylogenetic divergence in transcriptional capabilities that we present here. Having positioned the constituent subunits by tagging and deletion, we propose a model of key interaction interfaces that reveals the structural basis for this difference in functional conservation. Together, our findings establish a framework for understanding the structure-function relationships of the XPC complex in the interplay between transcription and DNA repair.