Regional Gene Repression by DNA Double-Strand Breaks in G1 Phase Cells
Autor: | Caitlin E. Purman, Eugene M. Oltz, Patrick L. Collins, Harshath Gupta, Barry P. Sleckman, Sofia I. Porter, Ankita Saini |
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Rok vydání: | 2019 |
Předmět: |
DNA End-Joining Repair
DNA Repair DNA damage DNA repair cells genetic processes Biology DNA-binding protein Cell Line Mice 03 medical and health sciences 0302 clinical medicine Transcription (biology) Silencer Elements Transcriptional Transcriptional regulation Animals Humans DNA Breaks Double-Stranded Regulatory Elements Transcriptional Molecular Biology Gene 030304 developmental biology 0303 health sciences Cell Cycle fungi G1 Phase DNA Cell Biology Cell biology Chromatin DNA-Binding Proteins enzymes and coenzymes (carbohydrates) biological phenomena cell phenomena and immunity 030217 neurology & neurosurgery Research Article DNA Damage |
Zdroj: | Mol Cell Biol |
ISSN: | 1098-5549 |
Popis: | DNA damage responses (DDR) to double-strand breaks (DSBs) alter cellular transcription programs at the genome-wide level. Through processes that are less well understood, DSBs also alter transcriptional responses locally, which may be important for efficient DSB repair. Here, we developed an approach to elucidate the cis-acting responses to DSBs in G(1) phase cells. We found that DSBs within a gene body silence its expression, as well as the transcription of local undamaged genes at a distance defined by the spread of γ-H2AX from the DSB. Importantly, DSBs not only repress ongoing transcription but also block the inducible expression of regional genes. DSB-mediated transcriptional repression depends on DDR signaling but does not require the generation of inaccessible chromatin. Our findings demonstrate that in G(1) phase cells, DDR signaling establishes a robust and extensive region of transcriptional repression spreading from DSB sites and introduce an approach to study the mechanistic impact of targeted DNA breaks in nearly any chromatin environment. |
Databáze: | OpenAIRE |
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