The transcription fidelity factor GreA impedes DNA break repair

Homologous recombination repairs DNA double-strand breaks and must function even on actively transcribed DNA. Because break repair prevents chromosome loss, the completion of repair is expected to outweigh the transcription of broken templates. Yet, the interplay between DNA break repair and transcription processivity is unclear. Here we show that the transcription factor GreA inhibits break repair in Escherichia coli. GreA restarts backtracked RNA polymerase (RNAP) and hence promotes transcription fidelity. We report that removal of GreA results in dramatically enhanced break repair via the classical RecBCD-RecA pathway. Using a deep-sequencing method to measure chromosomal exonucleolytic degradation (XO-Seq), we demonstrate that the absence of GreA limits RecBCD-mediated resection. Our findings suggest that increased RNAP backtracking promotes break repair by instigating RecA loading by RecBCD, without the influence of canonical Chi signals. The idea that backtracked RNAP can stimulate recombination presents a DNA transaction conundrum: a transcription fidelity factor compromises genomic integrity.