Bon voyage: A transcriptional journey around DNA breaks

Abstract

DNA double-strand breaks (DSBs) affect chromatin integrity and impact DNA-dependent processes such as transcription. Several studies revealed that the transcription of genes located in close proximity to DSBs is transiently repressed. This is achieved through the establishment of either a transient repressive chromatin context or eviction of the RNA polymerase II complex from the damaged chromatin. While these mechanisms of transcription repression have been shown to affect the efficiency and accuracy of DSB repair, it became evident that the transcriptional state of chromatin before DSB formation also influences this process. Moreover, transcription can be initiated from DSB ends, generating long non-coding (lnc)RNAs that will be processed into sequence-specific double-stranded RNAs. These so-called DNA damage-induced (dd)RNAs dictate DSB repair by regulating the accumulation of DNA repair proteins at DSBs. Thus, a complex interplay between mechanisms of transcription activation and repression occurs at DSBs and affects their repair. Here we review our current understanding of the mechanisms that coordinate transcription and DSB repair to prevent genome instability arising from DNA breaks in transcribed regions.

Keywords: Chromatin modifications; DNA double-strand break; Homologous recombination; Initiation silencing and termination of transcription; Non-homologous end-joining; RNAPII.