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  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.
See also: SW Awwad et al
Transcription is a potential source of genome instability and needs to be turned off during repair of DNA damage . While bulky DNA lesions directly interfere with the progression of the transcription machinery, other lesions, like DSBs, inhibit transcription through complex and not yet fully elucidated mechanisms that involve the DNA damage sensor kinases ataxia telangiectasia mutated (ATM)  and DNA‐dependent protein kinase (DNA‐PK) , as well as poly(ADP‐ribose) polymerase (PARP) . These enzymatic activities promote transcription silencing at DSBs through the recruitment of repressive chromatin modifying complexes , , , . However, …
Subscribers, please sign in with your username and password.