한빛사논문
Daegyu Park 1,5, Woo-Chang Chung 1,5, Shuang Gong 1, Subramaniyam Ravichandran 2, Gwang Myeong Lee 1, Minji Han 1, Kyeong Kyu Kim 3,4 & Jin-Hyun Ahn 1,4,*
1Department of Microbiology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
2Department of Biology, Stanford University, Stanford, CA, USA.
3Department of Precision Medicine, Institute for Antimicrobial Resistance Research and Therapeutics, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
4Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
5These authors contributed equally: Daegyu Park, Woo-Chang Chung.
*Corresponding author: correspondence to Jin-Hyun Ahn
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.
논문정보
관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기