A Minimal Sequence for Left-Handed G-Quadruplex Formation

Blaž Bakalar (1) , Brahim Heddi (2, 1) , Emmanuelle Schmitt (3) , Yves Mechulam (3) , Anh Tuân Phan (1)

1 Nanyang Technological University [Singapour]
2 LBPA - Laboratoire de Biologie et de Pharmacologie Appliquée
3 BIOC - Laboratoire de Biochimie de l'Ecole polytechnique

Recently, we observed the first example of a left-handed G-quadruplex structure formed by natural DNA, named Z-G4. We analysed the Z-G4 structure and inspected its primary 28-nt sequence in order to identify motifs that convey the unique left-handed twist. Using circular dichroism spectroscopy, NMR spectroscopy, and X-ray crystallography, we revealed a minimal sequence motif of 12 nt (GTGGTGGTGGTG) for formation of the left-handed DNA G-quadruplex, which is found to be highly abundant in the human genome. A systematic analysis of thymine loop mutations revealed a moderate sequence tolerance, which would further broaden the space of sequences prone to left-handed G-quadruplex formation.

Mots clés: DNA structures; G-quadruplexes; X-ray diffraction; circular dichroism

Domaines: Biologie structurale [q-bio.BM]

Blaž Bakalar, Brahim Heddi, Emmanuelle Schmitt, Yves Mechulam, Anh Tuân Phan. A Minimal Sequence for Left-Handed G-Quadruplex Formation. Angewandte Chemie International Edition, 2019, 58 (8), pp.2331-2335. ⟨10.1002/anie.201812628⟩. ⟨hal-02164372⟩