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Proc Natl Acad Sci U S A. 2018 Jul 17;115(29):E6770-E6779. doi: 10.1073/pnas.1716581115. Epub 2018 Jul 2.

Mechanistic insights in transcription-coupled nucleotide excision repair of ribosomal DNA.

Author information

1
Institut NeuroMyoGène, CNRS UMR 5310, INSERM U1217, Université de Lyon, Université Claude Bernard Lyon 1, 69622 Villeurbanne CEDEX, France.
2
Institut de Pharmacologie et de Biologie Structurale, CNRS UMR 5089, Université Paul Sabatier, BP64182, F-31077 Toulouse, France.
3
Institut NeuroMyoGène, CNRS UMR 5310, INSERM U1217, Université de Lyon, Université Claude Bernard Lyon 1, 69622 Villeurbanne CEDEX, France; ambra.mari@univ-lyon1.fr.

Abstract

Nucleotide excision repair (NER) guarantees genome integrity against UV light-induced DNA damage. After UV irradiation, cells have to cope with a general transcriptional block. To ensure UV lesions repair specifically on transcribed genes, NER is coupled with transcription in an extremely organized pathway known as transcription-coupled repair. In highly metabolic cells, more than 60% of total cellular transcription results from RNA polymerase I activity. Repair of the mammalian transcribed ribosomal DNA has been scarcely studied. UV lesions severely block RNA polymerase I activity and the full transcription-coupled repair machinery corrects damage on actively transcribed ribosomal DNAs. After UV irradiation, RNA polymerase I is more bound to the ribosomal DNA and both are displaced to the nucleolar periphery. Importantly, the reentry of RNA polymerase I and the ribosomal DNA is dependent on the presence of UV lesions on DNA and independent of transcription restart.

KEYWORDS:

RNAP1 transcription; UV lesions; human ribosomal DNA; nucleolar organization; nucleotide excision repair

PMID:
29967171
PMCID:
PMC6055190
DOI:
10.1073/pnas.1716581115
[Indexed for MEDLINE]
Free PMC Article

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