The first crystal structures of hybrid and parallel four-tetrad intramolecular G-quadruplexes

Beseiso, Dana; Chen, Erin V.; McCarthy, Sawyer E.; Martin, Kailey N.; Gallagher, Elizabeth P.; Miao, Joanne; Yatsunyk, Liliya A.

doi:10.1093/nar/gkac091

Title: The first crystal structures of hybrid and parallel four-tetrad intramolecular G-quadruplexes

Journal Article · Fri Feb 25 00:00:00 EST 2022 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkac091· OSTI ID:1846461

Beseiso, Dana ^[1]; Chen, Erin V. ^[1]; McCarthy, Sawyer E. ^[1]; Martin, Kailey N. ^[1]; Gallagher, Elizabeth P. ^[1]; Miao, Joanne ^[1];

^[1]

Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave, Swarthmore, PA 19081, USA

Abstract G-quadruplexes (GQs) are non-canonical DNA structures composed of stacks of stabilized G-tetrads. GQs play an important role in a variety of biological processes and may form at telomeres and oncogene promoters among other genomic locations. Here, we investigate nine variants of telomeric DNA from Tetrahymena thermophila with the repeat (TTGGGG)n. Biophysical data indicate that the sequences fold into stable four-tetrad GQs which adopt multiple conformations according to native PAGE. Excitingly, we solved the crystal structure of two variants, TET25 and TET26. The two variants differ by the presence of a 3′-T yet adopt different GQ conformations. TET25 forms a hybrid [3 + 1] GQ and exhibits a rare 5′-top snapback feature. Consequently, TET25 contains four loops: three lateral (TT, TT, and GTT) and one propeller (TT). TET26 folds into a parallel GQ with three TT propeller loops. To the best of our knowledge, TET25 and TET26 are the first reported hybrid and parallel four-tetrad unimolecular GQ structures. The results presented here expand the repertoire of available GQ structures and provide insight into the intricacy and plasticity of the 3D architecture adopted by telomeric repeats from T. thermophila and GQs in general.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division; National Institutes of Health (NIH)

Grant/Contract Number:: AC02-06CH11357; P30 GM124165; 1R15CA208676-01A1; 1R15CA253134

OSTI ID:: 1846461

Alternate ID(s):: OSTI ID: 1863051

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Vol. 50 Journal Issue: 5; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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