A Damaged Genome's Transcriptional Landscape Through Multilayered Expression Profiling Around in Situ-mapped DNA Double-strand Breaks

Overview

Journal Nat Commun

Specialty Biology

Date 2017 Jun 1

PMID 28561034

Citations 65

Authors

Fabio Iannelli

Alessandro Galbiati

Ilaria Capozzo

Quan Nguyen

Brian Magnuson

Flavia Michelini

Giuseppina DAlessandro

Matteo Cabrini

Marco Roncador

Sofia Francia

Nicola Crosetto

Mats Ljungman

Piero Carninci

Fabrizio dAdda di Fagagna

Affiliations

Soon will be listed here.

Abstract

Of the many types of DNA damage, DNA double-strand breaks (DSBs) are probably the most deleterious. Mounting evidence points to an intricate relationship between DSBs and transcription. A cell system in which the impact on transcription can be investigated at precisely mapped genomic DSBs is essential to study this relationship. Here in a human cell line, we map genome-wide and at high resolution the DSBs induced by a restriction enzyme, and we characterize their impact on gene expression by four independent approaches by monitoring steady-state RNA levels, rates of RNA synthesis, transcription initiation and RNA polymerase II elongation. We consistently observe transcriptional repression in proximity to DSBs. Downregulation of transcription depends on ATM kinase activity and on the distance from the DSB. Our study couples for the first time, to the best of our knowledge, high-resolution mapping of DSBs with multilayered transcriptomics to dissect the events shaping gene expression after DSB induction at multiple endogenous sites.

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