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Nucleic Acids Res. 2015 Mar 11;43(5):2744-56. doi: 10.1093/nar/gkv148. Epub 2015 Feb 26.

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

Author information

1
Department of Radiation Oncology and Translational Oncology Program, University of Michigan, Ann Arbor, MI, USA Department of Microbiology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil.
2
Department of Radiation Oncology and Translational Oncology Program, University of Michigan, Ann Arbor, MI, USA Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
3
Department of Radiation Oncology and Translational Oncology Program, University of Michigan, Ann Arbor, MI, USA.
4
Department of Microbiology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil.
5
Department of Radiation Oncology and Translational Oncology Program, University of Michigan, Ann Arbor, MI, USA Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI, USA ljungman@umich.edu.

Abstract

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.

PMID:
25722371
PMCID:
PMC4357734
DOI:
10.1093/nar/gkv148
[Indexed for MEDLINE]
Free PMC Article

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