Wang Z, Svejstrup J Q, Feaver W J, Wu X, Kornberg R D, Friedberg E C
Department of Pathology, University of Texas Southwestern Medical Center, Dallas 75235.
Nature. 1994 Mar 3;368(6466):74-6. doi: 10.1038/368074a0.
Nucleotide-excision repair (NER) is an important cellular defence mechanism against mutagenesis and carcinogenesis. The essential yeast genes RAD3 (ref. 2) and SSL2 (RAD25), homologues of the human xeroderma pigmentosum genes XPD and XPB respectively, have been implicated in NER in yeast. The products of these genes are also subunits of (Rad3 protein) or associate with (Ssl2 protein) purified yeast RNA polymerase II transcription initiation factor b, the counterpart of human TFIIH. Rad3 and Ssl2 proteins may participate directly in NER. Alternatively, they may function exclusively as transcription factors that support NER by influencing the expression of other NER genes. Here we show that defective NER in rad3 mutant extracts can be specifically complemented by purified transcription factor b. Similarly, defective NER in ssl2 mutant extracts is corrected by purified factor b/Ssl2 complex. These results support a direct role of factor b during NER in yeast. Hence, factor b (TFIIH) has a dual role in transcription and NER.
核苷酸切除修复(NER)是一种重要的细胞防御机制,可抵御诱变和致癌作用。酿酒酵母中的必需基因RAD3(参考文献2)和SSL2(RAD25)分别是人着色性干皮病基因XPD和XPB的同源物,它们参与了酵母中的核苷酸切除修复。这些基因的产物也是纯化的酵母RNA聚合酶II转录起始因子b(人TFIIH的对应物)的亚基(Rad3蛋白)或与之相关(Ssl2蛋白)。Rad3和Ssl2蛋白可能直接参与核苷酸切除修复。或者,它们可能仅作为转录因子发挥作用,通过影响其他核苷酸切除修复基因的表达来支持核苷酸切除修复。在这里,我们表明,rad3突变体提取物中存在缺陷的核苷酸切除修复可以被纯化的转录因子b特异性互补。同样,ssl2突变体提取物中存在缺陷的核苷酸切除修复可以被纯化的因子b/Ssl2复合物纠正。这些结果支持了因子b在酵母核苷酸切除修复过程中的直接作用。因此,因子b(TFIIH)在转录和核苷酸切除修复中具有双重作用。