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R-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli

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  • Hallie Wimberly

    (1 Baylor Plaza, Houston, Texas 77030, USA
    Present address: Department of Pathology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA)

  • Chandan Shee

    (1 Baylor Plaza, Houston, Texas 77030, USA)

  • P. C. Thornton

    (1 Baylor Plaza, Houston, Texas 77030, USA)

  • Priya Sivaramakrishnan

    (1 Baylor Plaza, Houston, Texas 77030, USA)

  • Susan M. Rosenberg

    (1 Baylor Plaza, Houston, Texas 77030, USA
    Molecular Virology and Microbiology and the Dan L Duncan Cancer Center, Baylor College of Medicine)

  • P. J. Hastings

    (1 Baylor Plaza, Houston, Texas 77030, USA)

Abstract

Double-stranded DNA ends, often from replication, drive genomic instability, yet their origin in non-replicating cells is unknown. Here we show that transcriptional RNA/DNA hybrids (R-loops) generate DNA ends that underlie stress-induced mutation and amplification. Depleting RNA/DNA hybrids with overproduced RNase HI reduces both genomic changes, indicating RNA/DNA hybrids as intermediates in both. An Mfd requirement and inhibition by translation implicate transcriptional R-loops. R-loops promote instability by generating DNA ends, shown by their dispensability when ends are provided by I-SceI endonuclease. Both R-loops and single-stranded endonuclease TraI are required for end formation, visualized as foci of a fluorescent end-binding protein. The data suggest that R-loops prime replication forks that collapse at single-stranded nicks, producing ends that instigate genomic instability. The results illuminate how DNA ends form in non-replicating cells, identify R-loops as the earliest known mutation/amplification intermediate, and suggest that genomic instability during stress could be targeted to transcribed regions, accelerating adaptation.

Suggested Citation

  • Hallie Wimberly & Chandan Shee & P. C. Thornton & Priya Sivaramakrishnan & Susan M. Rosenberg & P. J. Hastings, 2013. "R-loops and nicks initiate DNA breakage and genome instability in non-growing Escherichia coli," Nature Communications, Nature, vol. 4(1), pages 1-11, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3115
    DOI: 10.1038/ncomms3115
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    Cited by:

    1. Yayun Zheng & Ruochen Chai & Tianmin Wang & Zeqi Xu & Yihui He & Ping Shen & Jintao Liu, 2024. "RNA polymerase stalling-derived genome instability underlies ribosomal antibiotic efficacy and resistance evolution," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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