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DNA strand breaks and gaps target retroviral intasome binding and integration

Author

Listed:
  • Gayan Senavirathne

    (The Ohio State University College of Medicine)

  • James London

    (The Ohio State University College of Medicine)

  • Anne Gardner

    (The Ohio State University College of Medicine)

  • Richard Fishel

    (The Ohio State University College of Medicine
    The James Comprehensive Cancer Center and Ohio State University)

  • Kristine E. Yoder

    (The Ohio State University College of Medicine
    The James Comprehensive Cancer Center and Ohio State University
    The Ohio State University)

Abstract

Retrovirus integration into a host genome is essential for productive infections. The integration strand transfer reaction is catalyzed by a nucleoprotein complex (Intasome) containing the viral integrase (IN) and the reverse transcribed (RT) copy DNA (cDNA). Previous studies suggested that DNA target-site recognition limits intasome integration. Using single molecule Förster resonance energy transfer (smFRET), we show prototype foamy virus (PFV) intasomes specifically bind to DNA strand breaks and gaps. These break and gap DNA discontinuities mimic oxidative base excision repair (BER) lesion-processing intermediates that have been shown to affect retrovirus integration in vivo. The increased DNA binding events targeted strand transfer to the break/gap site without inducing substantial intasome conformational changes. The major oxidative BER substrate 8-oxo-guanine as well as a G/T mismatch or +T nucleotide insertion that typically introduce a bend or localized flexibility into the DNA, did not increase intasome binding or targeted integration. These results identify DNA breaks or gaps as modulators of dynamic intasome-target DNA interactions that encourage site-directed integration.

Suggested Citation

  • Gayan Senavirathne & James London & Anne Gardner & Richard Fishel & Kristine E. Yoder, 2023. "DNA strand breaks and gaps target retroviral intasome binding and integration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42641-4
    DOI: 10.1038/s41467-023-42641-4
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    References listed on IDEAS

    as
    1. Nathan D. Jones & Miguel A. Lopez Jr & Jeungphill Hanne & Mitchell B. Peake & Jong-Bong Lee & Richard Fishel & Kristine E. Yoder, 2016. "Retroviral intasomes search for a target DNA by 1D diffusion which rarely results in integration," Nature Communications, Nature, vol. 7(1), pages 1-9, September.
    2. Zhiqi Yin & Ke Shi & Surajit Banerjee & Krishan K. Pandey & Sibes Bera & Duane P. Grandgenett & Hideki Aihara, 2016. "Crystal structure of the Rous sarcoma virus intasome," Nature, Nature, vol. 530(7590), pages 362-366, February.
    3. Anton Sabantsev & Robert F. Levendosky & Xiaowei Zhuang & Gregory D. Bowman & Sebastian Deindl, 2019. "Direct observation of coordinated DNA movements on the nucleosome during chromatin remodelling," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    4. Stephen Hare & Saumya Shree Gupta & Eugene Valkov & Alan Engelman & Peter Cherepanov, 2010. "Retroviral intasome assembly and inhibition of DNA strand transfer," Nature, Nature, vol. 464(7286), pages 232-236, March.
    5. Daniel P. Maskell & Ludovic Renault & Erik Serrao & Paul Lesbats & Rishi Matadeen & Stephen Hare & Dirk Lindemann & Alan N. Engelman & Alessandro Costa & Peter Cherepanov, 2015. "Structural basis for retroviral integration into nucleosomes," Nature, Nature, vol. 523(7560), pages 366-369, July.
    6. Marcus D. Wilson & Ludovic Renault & Daniel P. Maskell & Mohamed Ghoneim & Valerie E. Pye & Andrea Nans & David S. Rueda & Peter Cherepanov & Alessandro Costa, 2019. "Retroviral integration into nucleosomes through DNA looping and sliding along the histone octamer," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    7. Goedele N. Maertens & Stephen Hare & Peter Cherepanov, 2010. "The mechanism of retroviral integration from X-ray structures of its key intermediates," Nature, Nature, vol. 468(7321), pages 326-329, November.
    8. Willem Vanderlinden & Tine Brouns & Philipp U. Walker & Pauline J. Kolbeck & Lukas F. Milles & Wolfgang Ott & Philipp C. Nickels & Zeger Debyser & Jan Lipfert, 2019. "The free energy landscape of retroviral integration," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
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