Cloning of a human homolog of the yeast nucleotide excision repair gene MMS19 and interaction with transcription repair factor TFIIH via the XPB and XPD helicases
Cloning of a human homolog of the yeast nucleotide excision repair gene MMS19 and interaction with transcription repair factor TFIIH via the XPB and XPD helicases
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DOI：
10.1093/nar/28.22.4506
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发表时间：
2000-11-15
影响因子：
14.9
通讯作者：
Hoeijmakers, JHJ
中科院分区：
文献类型：
--
作者：
Seroz, T;Winkler, GS;Hoeijmakers, JHJ
核苷酸切除修复（NER）通过高度保守的“剪切-粘贴”反应去除紫外线诱导的光产物和许多其他DNA损伤，该反应涉及大约25个核心组分。此外，已经确定了一些其他蛋白质，它们在体外对NER是必不可少的，但在体内的作用尚未确定，可能在NER和其他细胞过程的界面起作用。一个有趣的例子是酿酒酵母Mms19蛋白，它在NER和RNA中具有未知的双重功能，具有聚合酶II转录。在这里，我们报道了人类同源基因haMMS19的克隆和鉴定，该基因编码一个1030个氨基酸的蛋白质，与酿酒葡萄球菌Mms19p具有26%的同源性和51%的相似性，并且具有惊人的相似大小。表达谱和核位置与修复功能一致。共免疫沉淀实验显示，hMMS19直接与NER转录因子TFIIH的XPB和XPD亚基相互作用，这些发现扩展了NER装置的保守性以及NER与基础转录之间的联系，表明hMMS19通过与XPB和XPD解旋酶相互作用来发挥其修复和转录功能。
Nucleotide excision repair (NER) removes UV-induced photoproducts and numerous other DNA lesions in a highly conserved 'cut-and-paste' reaction that involves approximately 25 core components. In addition, several other proteins have been identified which are dispensable for NER in vitro but have an undefined role in vivo and may act at the interface of NER and other cellular processes. An intriguing example is the Saccharomyces cerevisiae Mms19 protein that an unknown dual function in NER and RNA has polymeraser II transcription. Here we report the cloning:and: characterization of a human homolog, designated haMMS19, that encodes a 1030 amino acid protein with 26% identity and 51% similarity to S. cerevisiae Mms19p and with a strikingly similar size. The expression profile and nuclear location are consistent with a repair function. Co-immunoprecipitation experiments revealed that hMMS19 directly interacts with the XPB and XPD subunits of NER-transcription factor TFIIH, These findings extend the conservation of the NER apparatus and the link between NER and basal transcription and suggest that hMMS19 exerts its function in repair and transcription by interacting with:the XPB and XPD helicases.