NMR solution and X-ray crystal structures of a DNA molecule containing both right- and left-handed parallel-stranded G-quadruplexes

Fernaldo Richtia Winnerdy (1) , Blaž Bakalar (1) , Arijit Maity (1) , J Jeya Vandana (1) , Yves Mechulam (2) , Emmanuelle Schmitt (2) , Anh Tuân Phan (1)

1 Division of Mathematical Sciences, School of Physical and Mathematical Sciences, College of Science
2 BIOC - Laboratoire de Biochimie de l'Ecole polytechnique

Analogous to the B- and Z-DNA structures in double-helix DNA, there exist both right- and left-handed quadruple-helix (G-quadruplex) DNA. Numerous conformations of right-handed and a few left-handed G-quadruplexes were previously observed, yet they were always identified separately. Here, we present the NMR solution and X-ray crystal structures of a right- and left-handed hybrid G-quadruplex. The structure reveals a stacking interaction between two G-quadruplex blocks with different helical orientations and displays features of both right- and left-handed G-quadruplexes. An analysis of loop mutations suggests that single-nucleotide loops are preferred or even required for the left-handed G-quadruplex formation. The discovery of a right- and left-handed hybrid G-quadruplex further expands the polymorphism of G-quadruplexes and is potentially useful in designing a left-to-right junction in G-quadruplex engineering.

Domains: Cellular Biology; Molecular biology; Quantitative Methods [q-bio.QM]; Cancer

Fernaldo Richtia Winnerdy, Blaž Bakalar, Arijit Maity, J Jeya Vandana, Yves Mechulam, et al.. NMR solution and X-ray crystal structures of a DNA molecule containing both right- and left-handed parallel-stranded G-quadruplexes. Nucleic Acids Research, 2019, 47, pp.gkz349. ⟨10.1093/nar/gkz349⟩. ⟨hal-02163879⟩