Kow Y W, Wallace S S, Van Houten B
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington 05405.
Mutat Res. 1990 Mar;235(2):147-56. doi: 10.1016/0921-8777(90)90068-g.
The UvrABC nuclease complex recognizes a wide spectrum of DNA lesions including pyrimidine dimers, bulky chemical adducts and O6-methylguanine. In this study we have demonstrated that the UvrABC complex is also able to incise PM2 DNA containing the oxidative DNA lesion, thymine glycol. However, DNA containing dihydrothymine, a lesion with a similar structure to thymine glycol, was not incised. The UvrABC complex was also able to incise DNA containing reduced apurinic sites or apurinic sites modified with O-alkyl hydroxylamines, but not DNA containing apurinic sites or urea residues. In vivo, in the absence of base-excision repair, nucleotide excision repair was operable on phi X-174 RF transfecting DNA containing thymine glycols. The level of the repair was found to be directly related to the level of the UvrABC complex. Thus, UvrABC-mediated nucleotide excision repair appears to play a role in the repair of thymine glycol, an oxidative DNA-base lesion that is produced by ionizing radiation or formed during oxidative respiration.
UvrABC核酸酶复合物能识别多种DNA损伤,包括嘧啶二聚体、大分子化学加合物和O6-甲基鸟嘌呤。在本研究中,我们证明UvrABC复合物也能够切割含有氧化性DNA损伤——胸苷乙二醇的PM2 DNA。然而,含有二氢胸腺嘧啶(一种结构与胸苷乙二醇相似的损伤)的DNA未被切割。UvrABC复合物还能够切割含有还原型脱嘌呤位点或经O-烷基羟胺修饰的脱嘌呤位点的DNA,但不能切割含有脱嘌呤位点或尿素残基的DNA。在体内,在缺乏碱基切除修复的情况下,核苷酸切除修复可作用于转染含有胸苷乙二醇的φX-174 RF DNA。发现修复水平与UvrABC复合物的水平直接相关。因此,UvrABC介导的核苷酸切除修复似乎在胸苷乙二醇的修复中发挥作用,胸苷乙二醇是一种由电离辐射产生或在氧化呼吸过程中形成的氧化性DNA碱基损伤。