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RNA-mediated double-strand break repair by end-joining mechanisms

Author

Listed:
  • Youngkyu Jeon

    (Georgia Institute of Technology
    National Institutes of Health (NIH))

  • Yilin Lu

    (Georgia Institute of Technology)

  • Margherita Maria Ferrari

    (University of South Florida
    University of Manitoba)

  • Tejasvi Channagiri

    (University of South Florida)

  • Penghao Xu

    (Georgia Institute of Technology)

  • Chance Meers

    (Georgia Institute of Technology
    Columbia University Irving Medical Center)

  • Yiqi Zhang

    (Georgia Institute of Technology
    Ann & Robert H. Lurie Children’s Hospital of Chicago
    Northwestern University Feinberg School of Medicine)

  • Sathya Balachander

    (Georgia Institute of Technology
    Emory University)

  • Vivian S. Park

    (Tulane University of Medicine)

  • Stefania Marsili

    (Georgia Institute of Technology)

  • Zachary F. Pursell

    (Tulane University of Medicine)

  • Nataša Jonoska

    (University of South Florida)

  • Francesca Storici

    (Georgia Institute of Technology)

Abstract

Double-strand breaks (DSBs) in DNA are challenging to repair. Cells employ at least three DSB-repair mechanisms, with a preference for non-homologous end joining (NHEJ) over homologous recombination (HR) and microhomology-mediated end joining (MMEJ). While most eukaryotic DNA is transcribed into RNA, providing complementary genetic information, much remains unknown about the direct impact of RNA on DSB-repair outcomes and its role in DSB-repair via end joining. Here, we show that both sense and antisense-transcript RNAs impact DSB repair in a sequence-specific manner in wild-type human and yeast cells. Depending on its sequence complementarity with the broken DNA ends, a transcript RNA can promote repair of a DSB or a double-strand gap in its DNA gene via NHEJ or MMEJ, independently from DNA synthesis. The results demonstrate a role of transcript RNA in directing the way DSBs are repaired in DNA, suggesting that RNA may directly modulate genome stability and evolution.

Suggested Citation

  • Youngkyu Jeon & Yilin Lu & Margherita Maria Ferrari & Tejasvi Channagiri & Penghao Xu & Chance Meers & Yiqi Zhang & Sathya Balachander & Vivian S. Park & Stefania Marsili & Zachary F. Pursell & Nataša, 2024. "RNA-mediated double-strand break repair by end-joining mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51457-9
    DOI: 10.1038/s41467-024-51457-9
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    References listed on IDEAS

    as
    1. Havva Keskin & Ying Shen & Fei Huang & Mikir Patel & Taehwan Yang & Katie Ashley & Alexander V. Mazin & Francesca Storici, 2014. "Transcript-RNA-templated DNA recombination and repair," Nature, Nature, vol. 515(7527), pages 436-439, November.
    2. Anirban Chakraborty & Nisha Tapryal & Tatiana Venkova & Nobuo Horikoshi & Raj K. Pandita & Altaf H. Sarker & Partha S. Sarkar & Tej K. Pandita & Tapas K. Hazra, 2016. "Classical non-homologous end-joining pathway utilizes nascent RNA for error-free double-strand break repair of transcribed genes," Nature Communications, Nature, vol. 7(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

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