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Structure of Tetrahelical DNA Homopolymers Supports Quadruplex World Hypothesis.

ABSTRACT: We previously reported a tetrahelical monomolecular architecture of DNA, tmDNA, which employs G-quartets and an all-parallel GGGTGGGTGGGTGGG (G3T) quadruplex as the repeating unit. Based on thermodynamic and kinetic studies, we proposed that covalently joined (G3T) _n units formed an uninterrupted programmable homopolymer; however, structural evidence for the tmDNA architecture was lacking. Here, we used NMR spectroscopy of wild-type and single-inosine-substituted constructs to characterize both monomolecular (G3T)₂ and bimolecular quadruplex-Mg-coupled versions of tmDNA. The NMR results support an architecture consisting of uninterrupted stacked G-tetrads in both the monomolecular constructs and bimolecular assemblies. Taken together, these data support the formation of a stable programmable homopolymeric tmDNA architecture, which may have been a precursor to the modern-day Watson-Crick DNA duplex.

SUBMITTER: Lomidze L

PROVIDER: S-EPMC8829921 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Structure of Tetrahelical DNA Homopolymers Supports Quadruplex World Hypothesis.

Lomidze Levan L Yang Mengkun M Khutsishvili David D Metreveli Nunu N Musier-Forsyth Karin K Kankia Besik B

ACS omega 20220126 5

We previously reported a tetrahelical monomolecular architecture of DNA, tmDNA, which employs G-quartets and an all-parallel GGGTGGGTGGGTGGG (G3T) quadruplex as the repeating unit. Based on thermodynamic and kinetic studies, we proposed that covalently joined (G3T) n units formed an uninterrupted programmable homopolymer; however, structural evidence for the tmDNA architecture was lacking. Here, we used NMR spectroscopy of wild-type and single-inosine-substituted constructs to ...[more]

PMID: 35155924

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