Duplex formation in a G-quadruplex bulge
| Autor: | Thi Quynh Ngoc Nguyen, Kah Wai Lim, Anh Tuân Phan |
|---|---|
| Přispěvatelé: | School of Physical and Mathematical Sciences, NTU Institute of Structural Biology |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Circular dichroism Guanine Magnetic Resonance Spectroscopy AcademicSubjects/SCI00010 Base pair Double Stranded DNA Biology 010402 general chemistry G-quadruplex 01 natural sciences 03 medical and health sciences Structural Biology Bulge Chemistry [Science] Genetics Humans heterocyclic compounds Structural motif Base Pairing Guanine Quadruplex 030304 developmental biology 0303 health sciences Base Sequence Circular Dichroism DNA Solution structure 0104 chemical sciences G-Quadruplexes Crystallography Duplex (building) Biological significance Nucleic Acid Conformation |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| DOI: | 10.1093/nar/gkaa738 |
| Popis: | Beyond the consensus definition of G-quadruplex-forming motifs with tracts of continuous guanines, G-quadruplexes harboring bulges in the G-tetrad core are prevalent in the human genome. Here, we study the incorporation of a duplex hairpin within a bulge of a G-quadruplex. The NMR solution structure of a G-quadruplex containing a duplex bulge was resolved, revealing the structural details of the junction between the duplex bulge and the G-quadruplex. Unexpectedly, instead of an orthogonal connection the duplex stem was observed to stack below the G-quadruplex forming a unique quadruplex-duplex junction. Breaking up of the immediate base pair step at the junction, coupled with a narrowing of the duplex groove within the context of the bulge, led to a progressive transition between the quadruplex and duplex segments. This study revealed that a duplex bulge can be formed at various positions of a G-quadruplex scaffold. In contrast to a non-structured bulge, the stability of a G-quadruplex slightly increases with an increase in the duplex bulge size. A G-quadruplex structure containing a duplex bulge of up to 33 nt in size was shown to form, which was much larger than the previously reported 7-nt bulge. With G-quadruplexes containing duplex bulges representing new structural motifs with potential biological significance, our findings would broaden the definition of potential G-quadruplex-forming sequences. Nanyang Technological University National Research Foundation (NRF) Published version Singapore National Research Foundation Investigatorship [NRF-NRFI2017-09]; Nanyang Technological University grants (to A.T.P.). Funding for open access charge: Singapore National Research Foundation. |
| Databáze: | OpenAIRE |
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