Double‐strand breaks (DSBs) trigger rapid and transient transcription pause to prevent collisions between repair and transcription machineries at damage sites. Little is known about the mechanisms that ensure transcriptional block after DNA damage. Here, we reveal a novel role of the negative elongation factor NELF in blocking transcription activity nearby DSBs. We show that NELF‐E and NELF‐A are rapidly recruited to DSB sites. Furthermore, NELF‐E recruitment and its repressive activity are both required for switching off transcription at DSBs. Remarkably, using I‐SceI endonuclease and CRISPR‐Cas9 systems, we observe that NELF‐E is preferentially recruited, in a PARP1‐dependent manner, to DSBs induced upstream of transcriptionally active rather than inactive genes. Moreover, the presence of RNA polymerase II is a prerequisite for the preferential recruitment of NELF‐E to DNA break sites. Additionally, we demonstrate that NELF‐E is required for intact repair of DSBs. Altogether, our data identify the NELF complex as a new component in the DNA damage response.
Transcription pause following DNA damage avoids collisions between transcription and repair machineries. This study shows that NELF‐E is recruited, in a PARP1‐dependent manner, to DSBs nearby active genes to shutdown transcription and facilitate repair.
NELF‐E is a new component in the DNA damage response.
NELF‐E is preferentially recruited, in a PARP1‐dependent manner, to DSBs nearby transcriptionally active genes to shutdown transcription.
RNA polymerase II is required for the preferential recruitment of NELF‐E to DSBs.
NELF‐E is required for fine‐tuning DSB repair.
- Received August 9, 2016.
- Revision received February 7, 2017.
- Accepted February 8, 2017.
- © 2017 The Authors
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