Structure and Cooperative Interactions Between the Guanine Quadruplexes of the Promoter of Gallus gallus βA-Globin Gene
- Authors: Marilovtseva E.V1, Koshkina D.O2,3, Feofanov A.V2, Studitsky V.M2,4
-
Affiliations:
- The Mental Health Research Center
- Lomonosov Moscow State University
- Institute of Gene Biology, Russian Academy of Sciences
- Fox Chase Cancer Center
- Issue: Vol 70, No 5 (2025)
- Pages: 854-863
- Section: Molecular biophysics
- URL: https://cijournal.ru/0006-3029/article/view/695403
- DOI: https://doi.org/10.31857/S0006302925050021
- ID: 695403
Cite item
Abstract
Guanine quadruplexes are nucleic acid secondary structures present in the genomes of all eukaryotes, from yeast to mammals, where they play an important role in maintaining telomere integrity, creating TAD boundaries, and regulating transcription, alternative splicing, and translation. It was found that, contributing to the formation of a nucleosome-free region, guanine quadruplexes formed by two G-rich motifs inside the replication origin that is located within the βA-globin promoter in Gallus gallus, are necessary for the initiation of replication. In our work, circular dichroism spectroscopy was used to study the structures and dynamic properties of guanine quadruplexes formed by the βA-globin promoter/origin sequence in vitro. The data obtained show that quadruplexes located on the same DNA fragment are formed cooperatively, influencing the structures of each other and the entire DNA fragment on which they are located. These data suggest that the structures of guanine quadruplexes may be determined by their genomic environment, and also help explain some of the properties of quadruplexes observed in vivo.
About the authors
E. V Marilovtseva
The Mental Health Research CenterMoscow, Russia
D. O Koshkina
Lomonosov Moscow State University; Institute of Gene Biology, Russian Academy of SciencesFaculty of Biology Moscow, Russia; Moscow, Russia
A. V Feofanov
Lomonosov Moscow State University
Email: arfeofanov@yandex.ru
Faculty of Biology Moscow, Russia
V. M Studitsky
Lomonosov Moscow State University; Fox Chase Cancer Center
Email: vasily.snaditsky@fccc.edu
Faculty of Biology Moscow, Russia; Philadelphia, USA
References
- Leontis N. B. and Westhof E. Geometric nomenclature and classification of RNA base pairs. RNA, 7, 499–512, (2001). doi: 10.1017/S1355838201002515
- Ghosh A. and Bansal M. A glossary of DNA structures from A to Z. Acta Crystallogr. D Biol. Crystallogr., 59, 620–626 (2003). doi: 10.1107/S0907444903003251
- Burge S., Parkinson G. N., Hazel P., Todd A. K., and Neidle S. Quadruplex DNA: Sequence, topology and structure. Nucl. Acids Res., 34, 5402–5415 (2006). doi: 10.1093/NAR/GKL655
- Phan A.T., Kuryavyi V., Burge S., Neidle S., and Patel D. J. Structure of an unprecedented G-quadruplex scaffold in the human c-Kit promoter. J. Am. Chem. Soc., 129, 4386–4392 (2007). doi: 10.1021/JA068739H
- Bhattacharyya D., Arachchilage G. M., and Basu S. Metal cations in G-quadruplex folding and stability. Front. Chem., 4, (2016). doi: 10.3389/FCHEM.2016.00038
- Guédin A., Gros J., Alberti P., and Mergny J. L. How long is too long? Effects of loop size on G-quadruplex stability. Nucl. Acids Res., 38, 7858–7868 (2010). doi: 10.1093/NAR/GKQ639
- Agrawal P., Hatzakis E., Guo K., Carver M., and Yang D. Solution structure of the major G-quadruplex formed in the human VEGF promoter in K+: Insights into loop interactions of the parallel G-quadruplexes. Nucleic Acids Res 2013, 41, 10584–10592, doi: 10.1093/NAR/GKT784
- Pandey S., Agarwala P., and Maiti S. Effect of loops and G-quartets on the stability of RNA G-quadruplexes. J. Phys. Chem. B, 117, 6896–6905 (2013). doi: 10.1021/JP401739M
- Ma Y., Iida K., and Nagasawa K. Topologies of G-quadruplex: Biological functions and regulation by ligands. Biochem. Biophys. Res. Commun., 531, 3–17 (2020). doi: 10.1016/j.bbrc.2019.12.103
- Li Q. J., Tong X. J., Duan Y. M., and Zhou J. Q. Characterization of the intramolecular G-quadruplex promoting activity of Esri. FEBS Lett., 587, 659–665 (2013). doi: 10.1016/J.FEBSLET.2013.01.024
- Zhang L., Sui C., Yang W., and Luo Q. Amino acid transporters: Emerging roles in drug delivery for tumor-targeting therapy. Asian J. Pharm. Sci., 15, 192–206 (2020). doi: 10.1016/j.aips.2019.12.002
- Bryan T. M. G-quadruplexes at telomeres: Friend or foe? Molecules, 25 (16), 3686 (2020). doi: 10.3390/molecules25163686
- Shiekh S., Kodikara S. G., and Balci H. Structure, topology, and stability of multiple G-quadruplexes in long telomeric overhangs. J. Mol. Biol., 436 (1), 168205 (2024). doi: 10.1016/j.jmb.2023.168205
- Hou Y., Li F., Zhang R., Li S., Liu H., Qin Z. S., and Sun X. Integrative characterization of G-quadruplexes in the three-dimensional chromatin structure. Epigenetics, 14, 894–911 (2019). doi: 10.1080/1559294.2019.1621140
- Williams J. D., Housevova D., Johnson B. R., Dyniewski B., Berroyer A., French H., Barchie A. A., Bilbrey D. D., Demeis J. D., Ghee K. R., Hughes A. G., Kreitz N. W., McInnis C. H., Pudner S. C., Reeves M. N., Stahly A. N., Turcu A., Watters B. C., Daly G. T., Langley R. J., Gillespie M. N., Prakash A., Larson E. D., Kasukurthi M. V., Huang J., Jinks-Robertson S., and Borchert G. M. Characterization of long G4-rich enhancer-associated genomic regions engaging in a novel loop-loop “G4 Kissing” interaction. Nucl. Acids Res., 48, 5907–5925 (2020). doi: 10.1093/NAR/GKAA357
- Mao S. Q., Ghanbarian A. T., Spiegel J., Martinez Cuesta S., Beraldi D., Di Antonio M., Marsico G., Hänsel-Hertsch R., Tamahill D., and Balasubramanian S. DNA G-quadruplex structures mold the DNA methylome. Nat. Struct. Mol. Biol., 25, 951–957 (2018). doi: 10.1038/S41594-018-0131-8
- Berardinelli F., Tanori M., Muoto D., Buccarelli M., Di Masi A., Leone S., Ricci-Vitiani L., Pallini R., Mancuso M., and Antoccia A. G-Quadruplex ligand RHPS4 radiosensitizes glioblastoma xenograft in vivo through a differential targeting of bulky differentiated-and stem-cancer cells. J. Exp. Clin. Cancer Res., 38, 311 (2019). doi: 10.1186/S13046-019-1293-X
- Yang M., Carter S., Parmar S., Bunne D. D., Calabrese D. R., Liang X., Yazdani K., Xu M., Liu Z., Thiele C. J., and Schneekloch J. S. Targeting a noncanonical, hairpin-containing G-quadruplex structure from the MYCN gene. Nucl. Acids Res., 49, 7856–7869 (2021). doi: 10.1093/NAR/GKAB594
- Han Z. and Wen L. G.-Quadruplex in cancer energy metabolism: a potential therapeutic target. Biochim. Biophys. Acta Gen. Subj., 1869 (7), 130810 (2025). doi: 10.1016/j.bbagen.2025.130810
- Figueiredo J., Mergny J. L., and Cruz C. G.-Quadruplex ligands in cancer therapy: Progress, challenges, and clinical perspectives. Life Sci., 340, 122481 (2024). doi: 10.1016/j.lfs.2024.122481
- Bhattacharyya U., Bhatia T., Deshpande S. N., and Thelma B. K. Association of G-quadruplex variants with schizophrenia symptoms. Schizophr. Res., 243, 361–363 (2022). doi: 10.1016/j.schres.2021.06.008
- Mohaghegh P., Karow J. K., Brosn R. M., Bohr V. A., and Hickson I. D. The Bloom’s and Werner’s syndrome proteins are DNA structure-specific helicases. Nucl. Acids Res., 29, 2843–2849 (2001). doi: 10.1093/NAR/29.13.2843
- Alkhunazi E., Shaheen R., Bharti S. K., Joseph-George A. M., Chong K., Abdel-Salam G. M. H., Alowan M., Blaser S. I., Papsin, B. C., Butt, M., Hashem M., Martin N., Godoy R., Brosn R. M. Jr, Alkuraya F. S., and Chitayat D. Warsaw breakage syndrome: Further clinical and genetic delineation. Am. J. Med. Genet. A, 176, 2404–2418 (2018), doi: 10.1002/AJMG.A.40482
- van Schiel J. J. M., Faramarz A., Balk J. A., Stewart G. S., Cantelli E., Oostra A. B., Rootmans M. A., Parish J. L., de Almeida Esteves C., Dumic, K., Barisic I., Diderich K. E. M., van Siegtenhorst M. A., Mahlab M., Pisani F. M., Te Riele H., Ameziane N., Wolthuis R. M. F., and de Lange J. Warsaw breakage syndrome associated DDXII helicase resolves G-quadruplex structures to support sister chromatid cohesion. Nat. Commun., 11 (1), 4287 (2020). doi: 10.1038/S41467-020-18066-8
- Poulet-Benedetti J., Tonnerre-Doncarii C., Valton A. L., Laurent M., Gerard M., Barinova N., Parisis N., Massip, F., Picard F., and Prioleau M. N. Dimeric G-quadruplex motifs-induced NFRS determine strong replication origins in vertebrates. Nat. Commun., 14, 4843 (2023). doi: 10.1038/S41467-023-40441-4
- Borras L. and Huguelet P. Schizophrenia and beta-thalassemia: A genetic link? Psychiatry Res., 158, 260–261 (2008). doi: 10.1016/j.psychres.2007.11.001
- Jin Y., Cheng Y., Mi J., and Xu J. A rare case of schizophrenia coexistence with antiphospholipid syndrome, β-thalassemia, and monoclonal gammopathy of undetermined significance. Front. Psychiatry, 14, 1178247 (2023). doi: 10.3389/FPSYT.2023.1178247
- Del Villar-Guerra R., Gray R. D., and Chaires J. B. Characterization of quadruplex DNA structure by circular dichroism. Curr. Protoc. Nucl. Acid Chem., 68, 17.8.1–17.8.16 (2017). doi: 10.1002/CPNC.23
- Zacchia M., Abategiovanni M. L., Stratigis S., and Capasso G. Potassium: From physiology to clinical implications. Kidney Dis. (Basel), 2, 72–79 (2016). doi: 10.1159/000446268
- Schiavone D., Guilbaud G., Murat P., Papadopoulou C., Sarkies P., Prioleau M., Balasubramanian S., and Sale J. E. Determinants of G quadruplex-induced epigenetic instability in REV 1-deficient cells. EMBO J., 33, 2507–2520 (2014). doi: 10.15252/EMBI.201488398
- Valton A. L., Hassan-Zadeh V., Lema I., Boggetto N., Alberti P., Saintomé C., Riou J. F., and Prioleau M. N. G4 motifs affect origin positioning and efficiency in two vertebrate replicators. EMBO J., 33, 732–746 (2014). doi: 10.1002/EMBI.201387506
- del Villar-Guerra R., Trent J. O., and Chaires J. B. G-quadruplex secondary structure obtained from circular dichroism spectroscopy. Angew. Chem. Int. Ed. Engl., 57, 7171–7175 (2018). doi: 10.1002/ANIE.201709184
- Harkness R. W. and Mittermaier A. K. G-register exchange dynamics in guanine quadruplexes. Nucl. Acids Res., 44, 3481–3494 (2016). doi: 10.1093/NAR/GKW190
- Linke R., Limmer M., Juranek S. A., Heine A., and Paeschke K. The relevance of G-quadruplexes for DNA repair. Int. J. Mol. Sci., 22 (22), 12599 (2021). doi: 10.3390/IJMS222212599
Supplementary files




