Tartier L, Michalik V, Spotheim-Maurizot M, Rahmouni A R, Sabattier R, Charlier M
Centre de Biophysique Moléculaire, CNRS, Orléans, France.
Nucleic Acids Res. 1994 Dec 25;22(25):5565-70. doi: 10.1093/nar/22.25.5565.
Ionizing radiations induce various damages in DNA via the hydroxyl radical OH. generated by the radiolysis of water. We compare here the radiosensitivity of B- and Z-DNA, by using a Z-prone stretch included in a plasmid. In the supercoiled plasmid, the stretch is in the Z-form, whereas it is in the B-form when the plasmid is relaxed. Frank strand breaks (FSB) and alkali-revealed breaks (ARB) were located and quantified using sequencing gel electrophoresis. We show that B- and Z-DNA have the same mean sensitivity towards radiolytic attack, for both FSB and ARB. Nevertheless, the guanine sites are more sensitive, and the cytosine sites less sensitive in Z- than in B-DNA, leading to a characteristic signature of the Z-form. The comparison of experiments with the outcome of a Monte Carlo simulation of OH. radical attack suggests that transfer of initial damage from a guanine base to its attached sugar or the adjacent 3' cytosine is more important in Z-DNA than in B-DNA.
电离辐射通过水的辐射分解产生的羟基自由基OH在DNA中诱导各种损伤。我们在这里通过使用质粒中包含的易形成Z型的片段来比较B-DNA和Z-DNA的辐射敏感性。在超螺旋质粒中,该片段呈Z型,而当质粒松弛时,它呈B型。使用测序凝胶电泳定位并定量了单链断裂(FSB)和碱敏感断裂(ARB)。我们表明,对于FSB和ARB,B-DNA和Z-DNA对辐射分解攻击具有相同的平均敏感性。然而,Z-DNA中的鸟嘌呤位点比B-DNA中的更敏感,而胞嘧啶位点则较不敏感,从而导致Z型的特征性特征。将实验结果与OH自由基攻击的蒙特卡罗模拟结果进行比较表明,在Z-DNA中,初始损伤从鸟嘌呤碱基转移到其连接的糖或相邻的3'胞嘧啶比在B-DNA中更重要。