Transcription-Coupled DNA Double-Strand Break Repair: Active Genes Need Special Care

•Novel sequencing-based methods revealed that active genes are particularly prone to breakage.•In G2, homologous recombination is favored at active genes.•Other less characterized pathways may ensure robust sequence recovery at active genes particularly in G1.•Transcription is subjected to a complex and dynamic regulation at damaged genes.

For decades, it has been speculated that specific loci on eukaryotic chromosomes are inherently susceptible to breakage. The advent of high-throughput genomic technologies has now paved the way to their identification. A wealth of data suggests that transcriptionally active loci are particularly fragile and that a specific DNA damage response is activated and dedicated to their repair. Here, we review current understanding of the crosstalk between transcription and double-strand break repair, from the reasons underlying the intrinsic fragility of genes to the mechanisms that restore the integrity of damaged transcription units.

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