Duplex formation in a G-quadruplex bulge
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...
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| Format: | Journal Article |
| Language: | English |
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2021
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| Online Access: | https://hdl.handle.net/10356/146278 |
| _version_ | 1826115460128571392 |
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| author | Ngoc Nguyen, Thi Quynh Lim, Kah Wai Phan, Anh Tuân |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Ngoc Nguyen, Thi Quynh Lim, Kah Wai Phan, Anh Tuân |
| author_sort | Ngoc Nguyen, Thi Quynh |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T03:55:30Z |
| format | Journal Article |
| id | ntu-10356/146278 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T03:55:30Z |
| publishDate | 2021 |
| record_format | dspace |
| spelling | ntu-10356/1462782023-02-28T19:50:35Z Duplex formation in a G-quadruplex bulge Ngoc Nguyen, Thi Quynh Lim, Kah Wai Phan, Anh Tuân School of Physical and Mathematical Sciences NTU Institute of Structural Biology Science::Chemistry Double Stranded DNA Guanine Quadruplex 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. 2021-02-04T09:15:44Z 2021-02-04T09:15:44Z 2020 Journal Article Ngoc Nguyen, T. Q., Lim, K. W., & Phan, A. T. (2020). Duplex formation in a G-quadruplex bulge. Nucleic Acids Research, 48(18), 10567-10575. doi:10.1093/nar/gkaa738 0305-1048 https://hdl.handle.net/10356/146278 10.1093/nar/gkaa738 32960213 2-s2.0-85092749640 18 48 10567 10575 en NRF-NRFI2017-09 Nucleic Acids Research © 2020 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. application/pdf |
| spellingShingle | Science::Chemistry Double Stranded DNA Guanine Quadruplex Ngoc Nguyen, Thi Quynh Lim, Kah Wai Phan, Anh Tuân Duplex formation in a G-quadruplex bulge |
| title | Duplex formation in a G-quadruplex bulge |
| title_full | Duplex formation in a G-quadruplex bulge |
| title_fullStr | Duplex formation in a G-quadruplex bulge |
| title_full_unstemmed | Duplex formation in a G-quadruplex bulge |
| title_short | Duplex formation in a G-quadruplex bulge |
| title_sort | duplex formation in a g quadruplex bulge |
| topic | Science::Chemistry Double Stranded DNA Guanine Quadruplex |
| url | https://hdl.handle.net/10356/146278 |
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