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G-quadruplex as an essential structural element in cytomegalovirus replication origin

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Listed:
  • Daegyu Park

    (Sungkyunkwan University School of Medicine)

  • Woo-Chang Chung

    (Sungkyunkwan University School of Medicine)

  • Shuang Gong

    (Sungkyunkwan University School of Medicine)

  • Subramaniyam Ravichandran

    (Stanford University)

  • Gwang Myeong Lee

    (Sungkyunkwan University School of Medicine)

  • Minji Han

    (Sungkyunkwan University School of Medicine)

  • Kyeong Kyu Kim

    (Sungkyunkwan University School of Medicine
    Samsung Medical Center)

  • Jin-Hyun Ahn

    (Sungkyunkwan University School of Medicine
    Samsung Medical Center)

Abstract

G-quadruplex (G4) structures are found in eukaryotic cell replication origins, but their role in origin function remains unclear. In this study G4 motifs are found in the lytic DNA replication origin (oriLyt) of human cytomegalovirus (HCMV) and recombinant viruses show that a G4 motif in oriLyt essential region I (ER-I) is necessary for viral growth. Replication assays of oriLyt-containing plasmids and biochemical/biophysical analyses show that G4 formation in ER-I is crucial for viral DNA replication. G4 pull-down analysis identifies viral DNA replication factors, such as IE2, UL84, and UL44, as G4-binding proteins. In enzyme-linked immunosorbent assays, specific G4-binding ligands inhibit G4 binding by the viral proteins. The Epstein-Barr virus oriLyt core element also forms a stable G4 that could substitute for the oriLyt ER-I G4 in HCMV. These results demonstrate that viral G4s in replication origins represent an essential structural element in recruiting replication factors and might be a therapeutic target against viral infections.

Suggested Citation

  • Daegyu Park & Woo-Chang Chung & Shuang Gong & Subramaniyam Ravichandran & Gwang Myeong Lee & Minji Han & Kyeong Kyu Kim & Jin-Hyun Ahn, 2024. "G-quadruplex as an essential structural element in cytomegalovirus replication origin," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51797-6
    DOI: 10.1038/s41467-024-51797-6
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    1. Ilias Georgakopoulos-Soares & Guillermo E. Parada & Hei Yuen Wong & Ragini Medhi & Giulia Furlan & Roberto Munita & Eric A. Miska & Chun Kit Kwok & Martin Hemberg, 2022. "Alternative splicing modulation by G-quadruplexes," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Zbigniew Pietras & Magdalena A. Wojcik & Lukasz S. Borowski & Maciej Szewczyk & Tomasz M. Kulinski & Dominik Cysewski & Piotr P. Stepien & Andrzej Dziembowski & Roman J. Szczesny, 2018. "Dedicated surveillance mechanism controls G-quadruplex forming non-coding RNAs in human mitochondria," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    3. Paulina Prorok & Marie Artufel & Antoine Aze & Philippe Coulombe & Isabelle Peiffer & Laurent Lacroix & Aurore Guédin & Jean-Louis Mergny & Julia Damaschke & Aloys Schepers & Christelle Cayrou & Marie, 2019. "Involvement of G-quadruplex regions in mammalian replication origin activity," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
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