Urata H, Yamamoto K, Akagi M, Hiroaki H, Uesugi S
Osaka University of Pharmaceutical Sciences, Japan.
Biochemistry. 1989 Dec 12;28(25):9566-9. doi: 10.1021/bi00451a002.
It has been reported that ACA sequences in DNA are mutagenic hot spots in UV-induced mutagenesis and are sites of an alkali-sensitive lesion produced by UV irradiation. In order to characterize the UV-induced lesion of an ACA site, chemically synthesized trideoxyribonucleotide d(ApCpA) was irradiated with UV light and the alkali-sensitive photoproduct was isolated. The structure of this photoproduct was characterized as the trinucleotide containing 2-deoxyribonolactone at the internal residue by 2D DQF-COSY, FT-IR, FAB-MS, and chemical properties. It is known that this lesion is also produced by gamma-irradiation, neocarzinostatin, the 1,10-phenanthroline-copper complex, and hydrogen peroxide and is highly mutagenic because of its resistance to cleavage by certain apurinic/apyrimidinic (AP) endonucleases. Thus, 2-deoxyribonolactone may be one of the lethal DNA lesions induced by UV irradiation to organisms and one of the intermediates of UV-induced DNA strand breaks because the DNA strand is cleaved at this site with beta- and subsequent delta-elimination mechanisms.
据报道，DNA中的ACA序列是紫外线诱导诱变中的诱变热点，也是紫外线照射产生的碱敏感损伤位点。为了表征ACA位点的紫外线诱导损伤，用紫外线照射化学合成的三脱氧核糖核苷酸d(ApCpA)，并分离出碱敏感光产物。通过二维双量子滤波相关谱（2D DQF-COSY）、傅里叶变换红外光谱（FT-IR）、快原子轰击质谱（FAB-MS）和化学性质对该光产物的结构进行了表征，其结构为内部残基含有2-脱氧核糖内酯的三核苷酸。已知这种损伤也可由γ射线照射、新制癌菌素、1,10-菲咯啉-铜络合物和过氧化氢产生，并且由于其对某些脱嘌呤/脱嘧啶（AP）内切酶的切割具有抗性而具有高度诱变性。因此，2-脱氧核糖内酯可能是紫外线照射对生物体诱导的致死性DNA损伤之一，也是紫外线诱导DNA链断裂的中间体之一，因为DNA链在此位点通过β消除和随后的δ消除机制被切割。
