G-quadruplex as an essential structural element in cytomegalovirus replication origin.
Nat Commun
; 15(1): 7353, 2024 Aug 27.
Article
in En
| MEDLINE
| ID: mdl-39191758
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Viral Proteins
/
Virus Replication
/
DNA, Viral
/
Immediate-Early Proteins
/
Replication Origin
/
Cytomegalovirus
/
DNA Replication
/
G-Quadruplexes
Limits:
Humans
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Country of publication:
United kingdom