A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A
A new, tenth subunit of TFIIH is responsible for the DNA repair syndrome trichothiodystrophy group A
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DOI：
10.1038/ng1387
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发表时间：
2004-07-01
期刊：
影响因子：
30.8
通讯作者：
Vermeulen, W
中科院分区：
文献类型：
--
作者：
Giglia-Mari, G;Coin, F;Vermeulen, W
DNA修复缺陷型毛硫营养不良（TTD）是由DNA修复和转录因子TFIIH的XPD和XPB亚基突变引起的。在第三种形式的DNA修复缺陷TTD中，称为a组，编码TFIIH的9个亚基中没有一个携带突变；相反，整个复合物的稳态水平严重降低(1)。最近在酵母中发现了新的第10个TFIIH亚基（TFB5）(2)。在这里，我们描述了人类TFB5同源物的鉴定及其与人类TFIIH的关联。微量注射编码TFB5 （GTF2H5，也称为TTDA）的cDNA，纠正了TTD-A细胞的dna修复缺陷，我们在三个不相关的TTD-A家族中发现了该基因的三个功能性失活突变。GTF2H5基因产物对TFIIH水平有调控作用。鉴定与TTD-A有关的一个新的进化保守的TFIIH亚基，有助于深入了解TFIIH在转录、DNA修复和人类疾病中的功能。
DNA repair-deficient trichothiodystrophy (TTD) results from mutations in the XPD and XPB subunits of the DNA repair and transcription factor TFIIH. In a third form of DNA repair deficient TTD, called group A, none of the nine subunits encoding TFIIH carried mutations; instead, the steady-state level of the entire complex was severely reduced(1). A new, tenth TFIIH subunit (TFB5) was recently identified in yeast(2). Here, we describe the identification of the human TFB5 ortholog and its association with human TFIIH. Microinjection of cDNA encoding TFB5 (GTF2H5, also called TTDA) corrected the DNA-repair defect of TTD-A cells, and we identified three functional inactivating mutations in this gene in three unrelated families with TTD-A. The GTF2H5 gene product has a role in regulating the level of TFIIH. The identification of a new evolutionarily conserved subunit of TFIIH implicated in TTD-A provides insight into TFIIH function in transcription, DNA repair and human disease.