Recovery of RNA synthesis from the DHFR gene following UV-irradiation precedes the removal of photolesions from the transcribed strand

Recovery of RNA synthesis from the DHFR gene following UV-irradiation precedes the removal of photolesions from the transcribed strand
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DOI:
10.1093/carcin/20.3.395
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发表时间:
1999-03-01
期刊:
影响因子:
4.7
通讯作者:
Ljungman, M
Ljungman, M
中科院分区:
医学2区
文献类型:
--
作者:
Ljungman, M

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据认为,恢复的RNA合成后,紫外线照射是密切相关的去除紫外线诱导的损伤从转录链的活性基因。为了验证这一假设,在暴露于UV光(254 nm)后评估CHO细胞中DHFR基因内三个不同位置的新生RNA合成。使用体内RNA标记以及核连续技术,发现在20分钟内,来自基因中部和3 '端的RNA合成分别被抑制了约30%和70%。虽然DHFR基因5 ′-末端的RNA合成得到增强,但在UV孵育后30-45分钟内,基因中间部分的RNA合成完全恢复,而基因3 ′-末端的恢复较慢。与以前发表的数据相比,从这些细胞中的DHFR基因的5 '-一半的UV诱导的DNA损伤的去除动力学,它的结论是,RNA合成恢复显着更快地在这个区域比可以解释从转录链的光损伤的去除。因此,虽然RNA合成最初被抑制UV诱导的photolisions,结果表明,RNA聚合酶II能够绕过这些病变之前,他们的删除。
It is thought that recovery of RNA synthesis following UV-irradiation is closely related to the removal of UV-induced lesions from the transcribed strand of active genes. To test this hypothesis, nascent RNA synthesis from three different locations within the DHFR gene in CHO cells was assessed following exposure to UV light (254 nm), Using both in vivo RNA labeling as well as the nuclear run-on technique, it was found that RNA synthesis from the middle and the 3'-end of the gene was inhibited within 20 min by similar to 30 and 70%, respectively, while RNA synthesis from the 5'-end of the DHFR gene was enhanced, RNA synthesis from the middle portion of the gene fully recovered within 30-45 min of post-UV incubation, while recovery was slower from the 3'-end of the gene. Compared with previously published data for the kinetics of removal of UV-induced DNA lesions from the 5'-half of the DHFR gene in these cells, it is concluded that RNA synthesis resumed significantly faster in this region than could be accounted for by the removal of photolesions from the transcribed strand. Thus, although RNA synthesis was initially inhibited by UV-induced photolesions, the results suggest that RNA polymerase II was able to bypass these lesions prior to their removal.