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

Daegyu Park, Woo-Chang Chung, Shuang Gong, Subramaniyam Ravichandran, Gwang Myeong Lee, Minji Han, Kyeong Kyu Kim and Jin-Hyun Ahn ()
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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
Jin-Hyun Ahn: Sungkyunkwan University School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-51797-6

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