Spt4 modulates Rad26 requirement in transcription-coupled nucleotide excision repair
Spt4 modulates Rad26 requirement in transcription-coupled nucleotide excision repair
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DOI：
10.1093/emboj/19.23.6498
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发表时间：
2000-12-01
期刊：
影响因子：
11.4
通讯作者：
Brouwer, J
中科院分区：
文献类型：
--
作者：
Jansen, LET;den Dulk, H;Brouwer, J
核苷酸切除修复机制可以优先靶向转录序列中的病变。这种DNA修复模式被称为转录偶联修复（TCR）。在酵母中，Rad26蛋白是人类柯凯因综合征B蛋白的对应物，与TCR特异性相关。在酵母菌株基因缺失的全球基因组修复中，RAD26的缺失使细胞对紫外线敏感，并显示出TCR缺陷。使用全基因组诱变方法，我们发现SPT4基因的缺失抑制了rad26缺陷。我们发现，Spt4缺失对rad26缺陷的抑制是特异性的，并且是由TCR以与rad26无关的方式重新激活引起的。Spt4参与转录伸长的调控。这种调节的缺失导致转录本质上是对TCR有能力的。我们的研究结果表明，Rad26作为一种延长因子，使转录TCR能够胜任，其需求可以通过Spt4调节。
The nucleotide excision repair machinery can be targeted preferentially to lesions in transcribed sequences. This mode of DNA repair is referred to as transcription-coupled repair (TCR). In yeast, the Rad26 protein, which is the counterpart of the human Cockayne syndrome B protein, is implicated specifically in TCR. In a yeast strain genetically deprived of global genome repair, a deletion of RAD26 renders cells UV sensitive and displays a defect in TCR. Using a genome-wide mutagenesis approach, we found that deletion of the SPT4 gene suppresses the rad26 defect. We show that suppression by the absence of Spt4 is specific for a rad26 defect and is caused by reactivation of TCR in a Rad26-independent manner. Spt4 is involved in the regulation of transcription elongation. The absence of this regulation leads to transcription that is intrinsically competent for TCR. Our findings suggest that Rad26 acts as an elongation factor rendering transcription TCR competent and that its requirement can be modulated by Spt4.