@article{3025701,
    title = "Continuous transcription initiation guarantees robust repair of all transcribed genes and regulatory regions",
    author = "Liakos, A. and Konstantopoulos, D. and Lavigne, M.D. and Fousteri, M.",
    journal = "Nature Communications",
    year = "2020",
    volume = "11",
    number = "1",
    publisher = "Institute of Geographic Sciences and Natural Resources Research",
    issn = "2041-1723",
    doi = "10.1038/s41467-020-14566-9",
    keywords = "messenger RNA;  RNA polymerase II;  RNA;  RNA polymerase II, DNA;  gene;  genetic analysis;  genotoxicity;  pigment, Article;  controlled study;  DNA damage;  DNA damage response;  DNA template;  excision repair;  gene expression;  gene locus;  histone modification;  human;  nucleosome;  promoter region;  RNA synthesis;  transcription elongation;  transcription initiation;  transcription initiation site;  ultraviolet irradiation;  chromatin;  DNA damage;  DNA repair;  gene expression regulation;  genetic transcription;  genetics;  metabolism;  regulatory sequence;  transcription initiation site, Chromatin;  DNA Damage;  DNA Repair;  Gene Expression Regulation;  Humans;  Promoter Regions, Genetic;  Regulatory Sequences, Nucleic Acid;  RNA;  RNA Polymerase II;  Transcription Initiation Site;  Transcription, Genetic",
    abstract = "Inhibition of transcription caused by DNA damage-impaired RNA polymerase II (Pol II) elongation conceals a local increase in de novo transcription, slowly progressing from Transcription Start Sites (TSSs) to gene ends. Although associated with accelerated repair of Pol II-encountered lesions and limited mutagenesis, it is still unclear how this mechanism is maintained during genotoxic stress-recovery. Here we uncover a widespread gain in chromatin accessibility and preservation of the active H3K27ac mark after UV-irradiation. The concomitant increase in Pol II escape from promoter-proximal pause (PPP) sites of most active genes, PROMPTs and enhancer RNAs favors unrestrained initiation, as evidenced by the synthesis of nascent RNAs including start RNAs. Accordingly, drug-inhibition of PPP-release replenishes levels of pre-initiating Pol II at TSSs after UV. Our data show that such continuous engagement of Pol II molecules ensures maximal transcription-driven repair throughout expressed genes and regulatory loci. Importantly, revealing this unanticipated regulatory layer of UV-response provides physiological relevant traction to the emerging concept that Pol II initiation rate is determined by pause-release dynamics. © 2020, The Author(s)."
}