Human Ribosomal DNA and RNA Polymerase I Fate during UV-induced DNA Repair

Abstract : Nucleotide excision repair (NER) guarantees genome integrity and proper cellular functions against UV-induced DNA damage. After UV irradiation, one of the first burden cells have to cope with is a general transcriptional block caused by the stalling of RNA polymerase II (RNAP2) onto distorting UV lesions. To insure UV lesions repair specifically on transcribed genes, NER is coupled with transcription in an extremely organized pathway known as Transcription-Coupled Repair (TCR). Most of the knowledge about TCR has been gathered from RNAP2 transcription. However, in highly metabolic cells, more than 60% of total cellular transcription results from ribosomal DNA (rDNA) transcription, by the RNA polymerase I (RNAP1), which takes place in the nucleolus. Many nuclear proteins are excluded from the nucleolus and because of this some nucleolar processes cannot occur inside this structure. In order to be replicated and repaired rDNAs need to be displaced at the nucleolar periphery. Despite the importance of RNAP1 transcription, repair of the mammalian transcribed rDNA has been scarcely studied. Moreover, to the best of our knowledge no molecular mechanism has been proposed for rDNA displacement. Our study clearly demonstrated that the full TCR machinery is needed to repair UV-damaged rDNA and restart RNAP1 transcription. Our results show that UV lesions block RNAP1 transcription and that RNAP1 is firmly stalled onto rDNAs without being degraded. Our study also describes the displacement of the RNAP1/rDNA complex to the nucleolar periphery after UV irradiation and identifies both nuclear ß-actin and nuclear myosin I as factors required for this displacement
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Laurianne Daniel. Human Ribosomal DNA and RNA Polymerase I Fate during UV-induced DNA Repair. Molecular biology. Université de Lyon, 2017. English. ⟨NNT : 2017LYSE1093⟩. ⟨tel-02163065⟩

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