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Nat Commun. 2017 May 31;8:15656. doi: 10.1038/ncomms15656.

A damaged genome's transcriptional landscape through multilayered expression profiling around in situ-mapped DNA double-strand breaks.

Author information

1
IFOM, The FIRC Institute of Molecular Oncology, Via Adamello 16, 20139 Milan, Italy.
2
IGM (Istituto di Genetica Molecolare)-CNR (Consiglio Nazionale delle Ricerche). Via Abbiategrasso 207, 27100 Pavia, Italy.
3
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, 230-0045, Japan.
4
Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109, USA.
5
Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 65 Stockholm, Sweden.

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.

PMID:
28561034
PMCID:
PMC5499205
DOI:
10.1038/ncomms15656
[Indexed for MEDLINE]
Free PMC Article

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