Switching genes to silent mode near DNA double-strand breaks

Abstract

Transcription is tightly regulated in response to DNA damage. Rapid and transient pausing of RNA polymerase II (RNAPII) is indeed critical to restrict the production of aberrant transcripts from damaged loci and to prevent deleterious collisions between transcription and repair machineries. Yet, how DNA lesions signal to the transcription machinery to coordinate DNA repair with transcriptional silencing is not fully elucidated. In this issue of EMBO Reports, Awwad et al 1 bring a new piece to the puzzle by identifying the negative transcription elongation factor NELF as a critical player in this process. They demonstrate that NELF is recruited to DNA double‐strand breaks (DSBs) near transcriptionally active genes in a poly(ADP‐ribose)‐ and RNAPII‐dependent manner to promote transcriptional repression and facilitate DSB repair.

Figure 1. Model for NELF‐mediated transcriptional silencing near DSBs

Upon DSB induction near a transcriptionally active gene, PARP1 modifies RNAPII (1), which in turn recruits a NELF subcomplex comprising NELF‐A and E subunits (2). NELF blocks transcription elongation (3), thus facilitating DSB repair (4).