The transcription fidelity factor GreA impedes DNA break repair

Priya Sivaramakrishnan, Leonardo A. Sepúlveda, Jennifer A. Halliday, Jingjing Liu, María Angélica Bravo Núñez, Ido Golding, Susan M. Rosenberg, Christophe Herman

Research output: Contribution to journalArticle

Abstract

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. However, 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 and hence promotes transcription fidelity. We report that removal of GreA results in markedly enhanced break repair via the classic RecBCD-RecA pathway. Using a deep-sequencing method to measure chromosomal exonucleolytic degradation, we demonstrate that the absence of GreA limits RecBCD-mediated resection. Our findings suggest that increased RNA polymerase backtracking promotes break repair by instigating RecA loading by RecBCD, without the influence of canonical Chi signals. The idea that backtracked RNA polymerase can stimulate recombination presents a DNA transaction conundrum: A transcription fidelity factor that compromises genomic integrity.

Original languageEnglish (US)
Pages (from-to)214-218
Number of pages5
JournalNature
Volume550
Issue number7675
DOIs
StatePublished - Oct 12 2017
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'The transcription fidelity factor GreA impedes DNA break repair'. Together they form a unique fingerprint.

  • Cite this

    Sivaramakrishnan, P., Sepúlveda, L. A., Halliday, J. A., Liu, J., Núñez, M. A. B., Golding, I., Rosenberg, S. M., & Herman, C. (2017). The transcription fidelity factor GreA impedes DNA break repair. Nature, 550(7675), 214-218. https://doi.org/10.1038/nature23907