In TFIIH the Arch domain of XPD is mechanistically essential for transcription and DNA repair
In TFIIH the Arch domain of XPD is mechanistically essential for transcription and DNA repair
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DOI：
10.1038/s41467-020-15241-9
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发表时间：
2020-04-03
影响因子：
16.6
通讯作者：
Kisker, Caroline
中科院分区：
文献类型：
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作者：
Peissert, Stefan;Sauer, Florian;Kisker, Caroline
XPD解旋酶是通用转录因子TFIIH的核心组成部分，在转录和核苷酸切除修复（NER）中起主要作用。在这里，我们展示了XPD的Arch结构域及其相互作用伙伴MAT1的高分辨率晶体结构，MAT1是CDK激活激酶复合物的核心成分。对界面的分析导致对MAT1-XPD相互作用至关重要的氨基酸残基的鉴定。更重要的是，Arch结构域的突变表明，这些残基通过损害XPD解旋酶活性或XPD与XPG的相互作用，对NER活性的调节至关重要；（ii） RNA聚合酶ii的磷酸化和RNA合成。我们的研究结果揭示了MAT1如何屏蔽这些功能上重要的残基，从而深入了解了MAT1如何调节XPD，并将Arch结构域定义为XPD支架中的主要机制参与者。
The XPD helicase is a central component of the general transcription factor TFIIH which plays major roles in transcription and nucleotide excision repair (NER). Here we present the high-resolution crystal structure of the Arch domain of XPD with its interaction partner MAT1, a central component of the CDK activating kinase complex. The analysis of the interface led to the identification of amino acid residues that are crucial for the MAT1-XPD interaction. More importantly, mutagenesis of the Arch domain revealed that these residues are essential for the regulation of (i) NER activity by either impairing XPD helicase activity or the interaction of XPD with XPG; (ii) the phosphorylation of the RNA polymerase II and RNA synthesis. Our results reveal how MAT1 shields these functionally important residues thereby providing insights into how XPD is regulated by MAT1 and defining the Arch domain as a major mechanistic player within the XPD scaffold.