Topological rules and anomalies in intramolecular G-quadruplex folding: a comprehensive study
Abstract
G-quadruplexes (G4s) make knots in DNA and RNA. One-block G4s can adopt eight different topologies, yet their folding rules are not precisely known. A systematic study of 353 intramolecular G4s enabled us to establish certain characteristics that rule their topology. In the absence of restraints imposed by a ligand or modified guanosines, when two loops are one nucleotide-long (nt), the topology is parallel, regardless of the third loop length. When loops 1 and 3 are 2-nt long, loop 2 length (L 2 ) determines the G4 topology: parallel for L 2 = 1, parallel or antiparallelchair for L 2 = 2, antiparallel-chair for L 2 = 3, and antiparallel-basket for L 2 = 4-5 nts. Diagonal loops require at least 4 nts; the only three structures with a diagonal loop of 3 nts present multiple anomalies. Only three topologies can accommodate a diagonal loop; the other five cannot. This shows the import ance of distinguishing bet ween the eight different topologies. We explain why parallel and hybrid topologies form preferentially three-tetrad G4s, while antiparallel topologies form preferentially two-tetrad G4s. We also explain why bulges between the G4 stem and the hairpin loop in quadruplex-duplex hybrids are sometimes needed. These findings clarify G4 folding principles and topological restraints.
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BibTeX
@article{granzhan2026topological,
title = {{Topological rules and anomalies in intramolecular G-quadruplex folding: a comprehensive study}},
author = {Anton Granzhan and Liliane Mouawad},
journal = {Nucleic Acids Research},
year = {2026},
month = may,
doi = {10.1093/nar/gkag435},
url = {https://hal.science/hal-05857469v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Topological rules and anomalies in intramolecular G-quadruplex folding: a comprehensive study
AU - Anton Granzhan
AU - Liliane Mouawad
PY - 2026
DA - 2026/05/19
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag435
UR - https://hal.science/hal-05857469v1
AB - G-quadruplexes (G4s) make knots in DNA and RNA. One-block G4s can adopt eight different topologies, yet their folding rules are not precisely known. A systematic study of 353 intramolecular G4s enabled us to establish certain characteristics that rule their topology. In the absence of restraints imposed by a ligand or modified guanosines, when two loops are one nucleotide-long (nt), the topology is parallel, regardless of the third loop length. When loops 1 and 3 are 2-nt long, loop 2 length (L 2 ) determines the G4 topology: parallel for L 2 = 1, parallel or antiparallelchair for L 2 = 2, antiparallel-chair for L 2 = 3, and antiparallel-basket for L 2 = 4-5 nts. Diagonal loops require at least 4 nts; the only three structures with a diagonal loop of 3 nts present multiple anomalies. Only three topologies can accommodate a diagonal loop; the other five cannot. This shows the import ance of distinguishing bet ween the eight different topologies. We explain why parallel and hybrid topologies form preferentially three-tetrad G4s, while antiparallel topologies form preferentially two-tetrad G4s. We also explain why bulges between the G4 stem and the hairpin loop in quadruplex-duplex hybrids are sometimes needed. These findings clarify G4 folding principles and topological restraints.
SN - 0305-1048
SN - 1362-4962
ER -