TFIIH controls developmentally-regulated cell cycle progression as a holocomplex
TFIIH controls developmentally-regulated cell cycle progression as a holocomplex
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DOI：
10.1111/j.1365-2443.2007.01133.x
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发表时间：
2007-11-01
期刊：
影响因子：
2.1
通讯作者：
Hiromi, Yasushi
中科院分区：
文献类型：
--
作者：
Matsuno, Motomi;Kose, Hiroyuki;Hiromi, Yasushi
基础转录因子，TFIIH，是一种多功能复合体，不仅具有转录功能，还具有DNA修复和细胞周期调控功能。TFIIH由两个亚复合体组成：核心TFIIH和CDK激活激酶(CAK)。体外研究表明，CAK对细胞周期调节是足够的，而核心TFIIH是DNA修复所必需的。然而，在体内执行这些功能的TFIIH复合体尚未确定。在这里，我们通过描述果蝇核心亚单位p52的突变来进行体内TFIIH活性的剖析。P52突变体对紫外线高度敏感，表明DNA修复存在缺陷。尽管如此，突变细胞能够分裂并表达各种分化标记。虽然p52对细胞周期进程本身并不是必不可少的，但眼睛想象盘中的p52突变细胞无法同步它们的细胞周期，并停留在G1期。在另一个核心亚单位XPB和CAK组分CDK7的突变中也观察到了相似的细胞周期表型，这表明核心TFIIH的缺陷通过改变CAK活性影响了G1/S的转变。我们认为，在发育过程中，TFIIH作为细胞周期调节因子的功能是由holo-TFIIH实现的。
Basal transcription factor, TFIIH, is a multifunctional complex that carries out not only transcription but also DNA repair and cell cycle control. TFIIH is composed of two sub-complexes: core TFIIH and Cdk-activating kinase (CAK). In vitro studies suggest that CAK is sufficient for cell cycle regulation, whereas core TFIIH is required for DNA repair. However, the TFIIH complexes that perform these functions in vivo have yet to be identified. Here, we perform an in vivo dissection of TFIIH activity by characterizing mutations in a core subunit p52 in Drosophila. p52 mutants are hypersensitive to UV, suggesting a defect in DNA repair. Nonetheless, mutant cells are able to divide and express a variety of differentiation markers. Although p52 is not essential for cell cycle progression itself, p52 mutant cells in the eye imaginal disc are unable to synchronize their cell cycles and remain arrested at G1. Similar cell cycle phenotypes are observed in mutations in another core subunit XPB and a CAK-component CDK7, suggesting that defects in core TFIIH affect the G1/S transition through modification of CAK activity. We propose that during development the function of TFIIH as a cell cycle regulator is carried out by holo-TFIIH.