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

ABSTRACT: Background: Of the many types of DNA damage, DNA double-strand breaks (DSB) 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. Methods: 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. Results: We consistently observe transcriptional repression in proximity to DSBs. Downregulation of transcription depends on ATM kinase activity and it is sensitive to the distance from the DSB. Conclusions: Our study couples for the first time high-resolution mapping of DSBs with multilayered transcriptomics to dissect the events shaping gene expression after DSB induction at multiple endogenous sites.

ORGANISM(S): Homo sapiens

PROVIDER: GSE97589 | GEO | 2017/06/01

SECONDARY ACCESSION(S): PRJNA382378

REPOSITORIES: GEO

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