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Classical non-homologous end-joining pathway utilizes nascent RNA for error-free double-strand break repair of transcribed genes

Author

Listed:
  • Anirban Chakraborty

    (Sealy Center for Molecular Medicine, University of Texas Medical Branch)

  • Nisha Tapryal

    (Sealy Center for Molecular Medicine, University of Texas Medical Branch)

  • Tatiana Venkova

    (Sealy Center for Molecular Medicine, University of Texas Medical Branch)

  • Nobuo Horikoshi

    (The Houston Methodist Research Institute)

  • Raj K. Pandita

    (The Houston Methodist Research Institute)

  • Altaf H. Sarker

    (Lawrence Berkeley National Laboratory)

  • Partha S. Sarkar

    (University of Texas Medical Branch)

  • Tej K. Pandita

    (The Houston Methodist Research Institute)

  • Tapas K. Hazra

    (Sealy Center for Molecular Medicine, University of Texas Medical Branch)

Abstract

DNA double-strand breaks (DSBs) leading to loss of nucleotides in the transcribed region can be lethal. Classical non-homologous end-joining (C-NHEJ) is the dominant pathway for DSB repair (DSBR) in adult mammalian cells. Here we report that during such DSBR, mammalian C-NHEJ proteins form a multiprotein complex with RNA polymerase II and preferentially associate with the transcribed genes after DSB induction. Depletion of C-NHEJ factors significantly abrogates DSBR in transcribed but not in non-transcribed genes. We hypothesized that nascent RNA can serve as a template for restoring the missing sequences, thus allowing error-free DSBR. We indeed found pre-mRNA in the C-NHEJ complex. Finally, when a DSB-containing plasmid with several nucleotides deleted within the E. coli lacZ gene was allowed time to repair in lacZ-expressing mammalian cells, a functional lacZ plasmid could be recovered from control but not C-NHEJ factor-depleted cells, providing important mechanistic insights into C-NHEJ-mediated error-free DSBR of the transcribed genome.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13049
    DOI: 10.1038/ncomms13049
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    Cited by:

    1. Junho Kim & August Yue Huang & Shelby L. Johnson & Jenny Lai & Laura Isacco & Ailsa M. Jeffries & Michael B. Miller & Michael A. Lodato & Christopher A. Walsh & Eunjung Alice Lee, 2022. "Prevalence and mechanisms of somatic deletions in single human neurons during normal aging and in DNA repair disorders," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Nisha Tapryal & Anirban Chakraborty & Kaushik Saha & Azharul Islam & Lang Pan & Koa Hosoki & Ibrahim M. Sayed & Jason M. Duran & Joshua Alcantara & Vanessa Castillo & Courtney Tindle & Altaf H. Sarker, 2023. "The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. 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 & NataĊĦa, 2024. "RNA-mediated double-strand break repair by end-joining mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-24, December.

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