CPD damage recognition by transcribing RNA polymerase II
CPD damage recognition by transcribing RNA polymerase II
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DOI：
10.1126/science.1135400
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发表时间：
2007-02-09
期刊：
影响因子：
56.9
通讯作者：
Cramer, Patrick
中科院分区：
文献类型：
--
作者：
Brueckner, Florian;Hennecke, Ulrich;Cramer, Patrick
细胞使用转录偶联修复（TCR）来有效地消除DNA损伤，如紫外线诱导的环丁烷嘧啶二聚体（CPD）。在这里，我们提出了基于结构的机制，在真核TCR的第一步，CPD诱导的RNA聚合酶（Pol）II停滞。转录链中的CPD缓慢通过易位屏障并进入聚合酶活性位点。CPD 5 '-胸腺嘧啶然后指导尿苷错误掺入信使RNA，其阻断易位。用腺苷人工取代尿苷使CPD旁路成为可能;因此，Pol II失速需要CPD定向的错误掺入。在停滞的复合体中，病变是不可接近的，并且聚合酶构象是不变的。这与修复因子的非变构募集和在Pol II存在下切除含有损伤的DNA片段一致。
Cells use transcription-coupled repair (TCR) to efficiently eliminate DNA lesions such as ultraviolet light-induced cyclobutane pyrimidine dimers (CPDs). Here we present the structure-based mechanism for the first step in eukaryotic TCR, CPD-induced stalling of RNA polymerase (Pol)II. A CPD in the transcribed strand slowly passes a translocation barrier and enters the polymerase active site. The CPD 5'-thymine then directs uridine misincorporation into messenger RNA, which blocks translocation. Artificial replacement of the uridine by adenosine enables CPD bypass; thus, Pol II stalling requires CPD-directed misincorporation. In the stalled complex, the lesion is inaccessible, and the polymerase conformation is unchanged. This is consistent with nonallosteric recruitment of repair factors and excision of a lesion-containing DNA fragment in the presence of Pol II.