title: Express or repress? The transcriptional dilemma of damaged chromatin.
abstract: The fine modulation of transcriptional activity around DNA lesions is essential to carefully regulate the crosstalk between the activation of the DNA damage response, DNA repair and transcription, particularly when the lesion occurs next to actively transcribed genes. Recently, several studies have been carried out to investigate how DNA lesions impact on local transcription, but the emerging model remains incomplete. Transcription of genes around damaged DNA is actively downregulated by the DNA damage response through different mechanisms, which appear specific to the chromatin context, the type of DNA damage or its complexity. Intriguingly, emerging evidence also indicates that transcription of noncoding RNAs (ncRNAs) is induced at sites of DNA damage, producing small ncRNAs that are, in turn, required for a full DNA damage response activation. We discuss here these recent findings, highlighting the major unresolved questions in the field, and propose ways to reconcile these apparently contradictory observations.
authors.affiliation: Istituto di Genetica Molecolare, CNR - Consiglio Nazionale delle Ricerche, Pavia, Italy.|Scuola Universitaria Superiore IUSS Pavia, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Capozzo
authors.affiliation: IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Iannelli
authors.affiliation: Istituto di Genetica Molecolare, CNR - Consiglio Nazionale delle Ricerche, Pavia, Italy.|IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, Milan, Italy.
authors.forename: Sofia
authors.initials: S
authors.lastname: Francia
authors.affiliation: Istituto di Genetica Molecolare, CNR - Consiglio Nazionale delle Ricerche, Pavia, Italy.|IFOM Foundation - FIRC Institute of Molecular Oncology Foundation, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: d'Adda di Fagagna
mesh_terms: D000818:Animals; D002843:Chromatin / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D022661:RNA, Untranslated / Q000235:genetics; D014158:Transcription, Genetic; D015003:Yeasts / Q000235:genetics
chemical_list: D002843:Chromatin; D022661:RNA, Untranslated
keywords: DNA damage response; DNA double-strand breaks; RNA Polymerase II; chromatin; gene silencing; noncoding RNAs; transcription