Lin J J, Sancar A
Department of Biochemistry, School of Medicine, University of North Carolina, Chapel Hill 27599.
Biochemistry. 1989 Oct 3;28(20):7979-84. doi: 10.1021/bi00446a002.
Escherichia coli (A)BC excinuclease is the major enzyme responsible for removing bulky adducts, such as pyrimidine dimers and 6-4 photoproducts, from DNA. Mutants deficient in this enzyme are extremely sensitive to UV and UV-mimetic agents, but not to oxidizing agents, or ionizing radiation which damages DNA in part by generating active oxygen species. DNA glycosylases and AP1 endonucleases play major roles in repairing oxidative DNA damage, and thus it has been assumed that nucleotide excision repair has no role in cellular defense against damage by ionizing radiation and oxidative damage. In this study we show that the E. coli nucleotide excision repair enzyme (A)BC excinuclease removes from DNA the two major products of oxidative damage, thymine glycol and the baseless sugar (AP site). We conclude that nucleotide excision repair is an important cellular defense mechanism against oxidizing agents.
大肠杆菌(A)BC核酸外切酶是负责从DNA中去除诸如嘧啶二聚体和6-4光产物等大的加合物的主要酶。缺乏这种酶的突变体对紫外线和紫外线模拟剂极其敏感,但对氧化剂或部分通过产生活性氧物种而损伤DNA的电离辐射不敏感。DNA糖基化酶和AP1核酸内切酶在修复氧化性DNA损伤中起主要作用,因此一直认为核苷酸切除修复在细胞防御电离辐射和氧化损伤方面不起作用。在本研究中,我们表明大肠杆菌核苷酸切除修复酶(A)BC核酸外切酶可从DNA中去除氧化性损伤的两种主要产物,胸腺嘧啶乙二醇和无碱基糖(AP位点)。我们得出结论,核苷酸切除修复是细胞对抗氧化剂的一种重要防御机制。