DNAPKcs-dependent arrest of RNA polymerase II transcription in the presence of DNA breaks

Tibor Pankotai, Céline Bonhomme, David Chen, Evi Soutoglou

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

DNA double-strand break (DSB) repair interferes with ongoing cellular processes, including replication and transcription. Although the process of replication stalling upon collision of replication forks with damaged DNA has been extensively studied, the fate of elongating RNA polymerase II (RNAPII) that encounters a DSB is not well understood. We show that the occurrence of a single DSB at a human RNAPII-transcribed gene leads to inhibition of transcription elongation and reinitiation. Upon inhibition of DNA protein kinase (DNAPK), RNAPII bypasses the break and continues transcription elongation, suggesting that it is not the break per se that inhibits the processivity of RNAPII, but the activity of DNAPK. We also show that the mechanism of DNAPK-mediated transcription inhibition involves the proteasome-dependent pathway. The results point to the pivotal role of DNAPK activity in the eviction of RNAPII from DNA upon encountering a DNA lesion.

Original languageEnglish (US)
Pages (from-to)276-282
Number of pages7
JournalNature Structural and Molecular Biology
Volume19
Issue number3
DOIs
StatePublished - Mar 1 2012

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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