A Cytosine‑Bulged (3+1) Hybrid G‑Quadruplex Formed by the Chicken DNA Replication Origin.

Area of Science:

• Genomics
• Structural Biology
• Molecular Biology

Background:

• Guanine (G)-rich nucleic acid sequences form G-quadruplex (G4) structures.
• Origin G-rich repeated elements (OGRE) are found at replication origins across species.
• The G4 structures formed by OGRE are not well understood.

Purpose of the Study:

• To determine the high-resolution G4 structure formed by OGRE from the chicken β-globin replication origin.
• To investigate the structural features of this G4 and their potential implications.

Main Methods:

• High-resolution structural determination of the G4 formed by the ChOGRE23 DNA sequence.
• Analysis of the G4 structure, including glycosidic conformation and the presence of bulges.

Main Results:

• The ChOGRE23 sequence folds into an intramolecular three-layer (3+1) hybrid G4.
• The structure contains a cytosine bulge.
• An unusual anti glycosidic conformation was observed for a guanine in the outermost G-quartet.

Conclusions:

• The determined G4 structure of chicken OGRE reveals unique features, including a cytosine bulge and an unobserved glycosidic alignment.
• These structural characteristics may facilitate recognition by replication-associated proteins or small molecules.
• This study provides novel insights into the structural diversity of G4s formed by OGRE at replication origins.