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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.
Afiliação
  • Beseiso D; Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave, Swarthmore, PA 19081, USA.
  • Chen EV; Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave, Swarthmore, PA 19081, USA.
  • McCarthy SE; Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave, Swarthmore, PA 19081, USA.
  • Martin KN; Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave, Swarthmore, PA 19081, USA.
  • Gallagher EP; Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave, Swarthmore, PA 19081, USA.
  • Miao J; Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave, Swarthmore, PA 19081, USA.
  • Yatsunyk LA; Department of Chemistry and Biochemistry, Swarthmore College, 500 College Ave, Swarthmore, PA 19081, USA.
Nucleic Acids Res ; 50(5): 2959-2972, 2022 03 21.
Article em En | MEDLINE | ID: mdl-35212369
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quadruplex G Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quadruplex G Idioma: En Ano de publicação: 2022 Tipo de documento: Article