DNA repair and recovery of RNA synthesis following exposure to ultraviolet light are delayed in long genes.

DNA repair and recovery of RNA synthesis following exposure to ultraviolet light are delayed in long genes.
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DOI:
10.1093/nar/gkv148
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发表时间:
2015-03-11
影响因子:
14.9
通讯作者:
Ljungman M
Ljungman M
中科院分区:
生物学2区
文献类型:
--
作者:
Andrade-Lima LC;Veloso A;Paulsen MT;Menck CF;Ljungman M

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使用新生RNA Bru-seq和定量长PCR评估UV照射后人类细胞中DNA修复和RNA合成恢复的动力学。结果表明,紫外光抑制转录延长,RNA合成的恢复在5′-3′方向呈波浪状,恢复缓慢,长基因的3′端出现TC-NER。在野生型成纤维细胞中恢复24 h后,RNA合成在基因的3′端完全恢复,但在转录偶联核苷酸切除修复(TC-NER)或全局基因组NER(GG-NER)缺陷的细胞中则没有。不同的转录恢复曲线被发现为个别基因,但这些差异并不完全相关的差异,这些基因的DNA修复。我们的研究给出了第一个全基因组的观点,紫外线诱导的病变如何影响转录,以及如何恢复RNA合成的大基因是特别延迟的明显缺乏恢复转录被逮捕的聚合酶。
The kinetics of DNA repair and RNA synthesis recovery in human cells following UV-irradiation were assessed using nascent RNA Bru-seq and quantitative long PCR. It was found that UV light inhibited transcription elongation and that recovery of RNA synthesis occurred as a wave in the 5′-3′ direction with slow recovery and TC-NER at the 3′ end of long genes. RNA synthesis resumed fully at the 3′-end of genes after a 24 h recovery in wild-type fibroblasts, but not in cells deficient in transcription-coupled nucleotide excision repair (TC-NER) or global genomic NER (GG-NER). Different transcription recovery profiles were found for individual genes but these differences did not fully correlate to differences in DNA repair of these genes. Our study gives the first genome-wide view of how UV-induced lesions affect transcription and how the recovery of RNA synthesis of large genes are particularly delayed by the apparent lack of resumption of transcription by arrested polymerases.
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