DNA repair and recovery of RNA synthesis following exposure to ultraviolet light are delayed in long genes.
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.
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.
Leonardo C
LC
Andrade-Lima
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.
Artur
A
Veloso
Department of Radiation Oncology and Translational Oncology Program, University of Michigan, Ann Arbor, MI, USA.
Michelle T
MT
Paulsen
Department of Microbiology, Biomedical Sciences Institute, University of São Paulo, São Paulo, Brazil.
Carlos F M
CF
Menck
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.
Mats
M
Ljungman
D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000528:radiation effects*; D059467:Transcriptome / Q000528:radiation effects; D014466:Ultraviolet Rays
D012313:RNA; D004247:DNA