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

Fingerprint

DNA Breaks
DNA-Directed RNA Polymerases
DNA Repair
Transcription Factors
Recombinational DNA Repair
High-Throughput Nucleotide Sequencing
DNA
Genetic Recombination
Chromosomes
Escherichia coli

ASJC Scopus subject areas

  • General

Cite this

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

The transcription fidelity factor GreA impedes DNA break repair. / Sivaramakrishnan, Priya; Sepúlveda, Leonardo A.; Halliday, Jennifer A.; Liu, Jingjing; Núñez, María Angélica Bravo; Golding, Ido; Rosenberg, Susan M.; Herman, Christophe.

In: Nature, Vol. 550, No. 7675, 12.10.2017, p. 214-218.

Research output: Contribution to journalArticle

Sivaramakrishnan, P, Sepúlveda, LA, Halliday, JA, Liu, J, Núñez, MAB, Golding, I, Rosenberg, SM & Herman, C 2017, 'The transcription fidelity factor GreA impedes DNA break repair', Nature, vol. 550, no. 7675, pp. 214-218. https://doi.org/10.1038/nature23907
Sivaramakrishnan P, Sepúlveda LA, Halliday JA, Liu J, Núñez MAB, Golding I et al. The transcription fidelity factor GreA impedes DNA break repair. Nature. 2017 Oct 12;550(7675):214-218. https://doi.org/10.1038/nature23907
Sivaramakrishnan, Priya ; Sepúlveda, Leonardo A. ; Halliday, Jennifer A. ; Liu, Jingjing ; Núñez, María Angélica Bravo ; Golding, Ido ; Rosenberg, Susan M. ; Herman, Christophe. / The transcription fidelity factor GreA impedes DNA break repair. In: Nature. 2017 ; Vol. 550, No. 7675. pp. 214-218.
@article{810cfc57135745d0aeafd193c14064bc,
title = "The transcription fidelity factor GreA impedes DNA break repair",
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.",
author = "Priya Sivaramakrishnan and Sep{\'u}lveda, {Leonardo A.} and Halliday, {Jennifer A.} and Jingjing Liu and N{\'u}{\~n}ez, {Mar{\'i}a Ang{\'e}lica Bravo} and Ido Golding and Rosenberg, {Susan M.} and Christophe Herman",
year = "2017",
month = "10",
day = "12",
doi = "10.1038/nature23907",
language = "English (US)",
volume = "550",
pages = "214--218",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7675",

}

TY - JOUR

T1 - The transcription fidelity factor GreA impedes DNA break repair

AU - Sivaramakrishnan, Priya

AU - Sepúlveda, Leonardo A.

AU - Halliday, Jennifer A.

AU - Liu, Jingjing

AU - Núñez, María Angélica Bravo

AU - Golding, Ido

AU - Rosenberg, Susan M.

AU - Herman, Christophe

PY - 2017/10/12

Y1 - 2017/10/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85031303274&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031303274&partnerID=8YFLogxK

U2 - 10.1038/nature23907

DO - 10.1038/nature23907

M3 - Article

C2 - 28976965

AN - SCOPUS:85031303274

VL - 550

SP - 214

EP - 218

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7675

ER -