Regional gene repression by DNA double-strand breaks in G1 phase cells

Caitlin E. Purman, Patrick L. Collins, Sofia I. Porter, Ankita Saini, Harshath Gupta, Barry P. Sleckman, Eugene M. Oltz

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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 G1 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 G1 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.

Original languageEnglish
Article numbere00181-19
JournalMolecular and cellular biology
Volume39
Issue number24
DOIs
StatePublished - Dec 1 2019

Keywords

  • Chromatin
  • DNA damage
  • DNA damage signaling
  • Nonhomologous DNA end joining
  • Transcriptional regulation

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    Purman, C. E., Collins, P. L., Porter, S. I., Saini, A., Gupta, H., Sleckman, B. P., & Oltz, E. M. (2019). Regional gene repression by DNA double-strand breaks in G1 phase cells. Molecular and cellular biology, 39(24), [e00181-19]. https://doi.org/10.1128/MCB.00181-19