Sweder K S, Chun R, Mori T, Hanawalt P C
Department of Biological Sciences, Stanford University, CA 94305-5020, USA.
Nucleic Acids Res. 1996 Apr 15;24(8):1540-6. doi: 10.1093/nar/24.8.1540.
Several proteins, including Rad3 and Rad25(Ssl2), are essential for nucleotide excision repair (NER) and function in the RNA polymerase II transcription initiation complex TFIIH. Mutations in genes encoding two other subunits of TFIIH, TFB1 and SSL1, result in UV sensitivity and have been shown to take part in NER in an in vitro system. However, a deficiency in global NER does not exclude the possibility that such repair-deficient mutants can perform transcription-coupled repair (TCR), as shown for xeroderma pigmentosum group C. To date, temperature-sensitive C-terminal truncations of Tfbl are the only TFIIH mutations that result in intermediate UV sensitivity, which might indicate a deficiency in either the global NER or TCR pathways. We have directly analyzed both TCR and global NER in these mutants. We found that ssl1, rad3 and tfb1 mutants, like rad25(ssl2-xp) mutants, are deficient in both the global NER and TCR pathways. Our results support the view that the mutations in any one of the genes encoding subunits of TFIIH result in deficiencies in both global and TCR pathways of NER. We suggest that when subunits of TFIIH are in limiting amounts, TCR may preclude global NER.
包括Rad3和Rad25（Ssl2）在内的几种蛋白质对于核苷酸切除修复（NER）至关重要，并在RNA聚合酶II转录起始复合物TFIIH中发挥作用。编码TFIIH另外两个亚基TFB1和SSL1的基因突变会导致对紫外线敏感，并且已证实在体外系统中参与NER。然而，整体NER缺陷并不排除此类修复缺陷型突变体能够进行转录偶联修复（TCR）的可能性，如着色性干皮病C组所示。迄今为止，Tfbl的温度敏感型C末端截短是导致中等程度紫外线敏感性的唯一TFIIH突变，这可能表明整体NER或TCR途径存在缺陷。我们直接分析了这些突变体中的TCR和整体NER。我们发现，ssl1、rad3和tfb1突变体与rad25（ssl2-xp）突变体一样，在整体NER和TCR途径中均存在缺陷。我们的结果支持这样一种观点，即编码TFIIH亚基的任何一个基因突变都会导致NER的整体和TCR途径出现缺陷。我们认为，当TFIIH亚基数量有限时，TCR可能会排除整体NER。
