Leadon S A, Dunn A B, Ross C E
Department of Radiation Oncology, University of North Carolina at Chapel Hill 27599-7512, USA.
Radiat Res. 1996 Aug;146(2):123-30.
We have discovered a novel DNA repair response which is induced in cells irradiated with gamma rays at the G1/S-phase border. The induction of this repair response occurs at a stage in the cell cycle when overall levels of excision repair are reduced compared to cells irradiated in either S phase, G2/M phase or exponential growth. The induced repair is characterized by the formation of very long excision repair patches (VLERP) containing at least 150 nucleotides compared to the constitutive repair patches that are 3-5 nucleotides. These VLERP appear to be produced in response to a DNA lesion specific to ionizing radiation since they were not observed in cells irradiated with UV radiation at G1/S phase. The formation of VLERP requires both the nucleotide excision repair pathway, since they are absent in irradiated xeroderma pigmentosum group A cells, and the synthesis of new protein and mRNA. The time course for the induction of the VLERP shows an initial delay of 2 h, followed by a steady increase for up to 12 h after irradiation. By comparison, the production of the constitutive short repair patches shows an initial rapid production which levels out after 4 h.
我们发现了一种新的DNA修复反应,它在处于G1/S期边界的γ射线照射细胞中被诱导。这种修复反应的诱导发生在细胞周期的一个阶段,与在S期、G2/M期或指数生长期照射的细胞相比,此时切除修复的总体水平降低。诱导修复的特征是形成非常长的切除修复片段(VLERP),其包含至少150个核苷酸,而组成型修复片段为3-5个核苷酸。这些VLERP似乎是对电离辐射特有的DNA损伤作出的反应,因为在G1/S期用紫外线照射的细胞中未观察到它们。VLERP的形成既需要核苷酸切除修复途径,因为在照射的A型着色性干皮病细胞中不存在VLERP,也需要新蛋白质和mRNA的合成。VLERP诱导的时间进程显示最初延迟2小时,随后在照射后长达12小时稳定增加。相比之下,组成型短修复片段的产生显示最初快速产生,在4小时后趋于平稳。