3 years ago

Express or repress? The transcriptional dilemma of damaged chromatin

Express or repress? The transcriptional dilemma of damaged chromatin
Fabrizio d'Adda di Fagagna, Fabio Iannelli, Ilaria Capozzo, Sofia Francia
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. DNA double-strand breaks (DSBs) generation within actively transcribed regions elicits a complex transcriptional response in cis to the lesion that favors DSB repair. This causes both transcriptional repression of damaged genes and the biogenesis of DSB-induced small noncoding RNAs. Here, we discuss the modulation of transcription at DSBs and its tight connection with the activation of the DNA damage response.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/febs.14048

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