Structure of native four-repeat satellite III sequence with non-canonical base interactions

Abstract Tandem-repetitive DNA (where two or more DNA bases are repeated numerous times) can adopt non-canonical secondary structures. Many of these structures are implicated in important biological processes. Human Satellite III (HSat3) is enriched for tandem repeats of the sequence ATGGA and is lo...

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Bibliographic Details
Published in:Nucleic acids research 2024-04, Vol.52 (6), p.3390-3405
Main Authors: Chen, Erin, Trajkovski, Marko, Lee, Hyun Kyung, Nyovanie, Samantha, Martin, Kailey N, Dean, William L, Tahiliani, Mamta, Plavec, Janez, Yatsunyk, Liliya A
Format: Article
Language:English
Subjects:
Base Sequence
DNA - chemistry
DNA - genetics
Guanine - chemistry
Humans
Nucleic Acid Conformation
Repetitive Sequences, Nucleic Acid
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Summary:Abstract Tandem-repetitive DNA (where two or more DNA bases are repeated numerous times) can adopt non-canonical secondary structures. Many of these structures are implicated in important biological processes. Human Satellite III (HSat3) is enriched for tandem repeats of the sequence ATGGA and is located in pericentromeric heterochromatin in many human chromosomes. Here, we investigate the secondary structure of the four-repeat HSat3 sequence 5′-ATGGA ATGGA ATGGA ATGGA-3′ using X-ray crystallography, NMR, and biophysical methods. Circular dichroism spectroscopy, thermal stability, native PAGE, and analytical ultracentrifugation indicate that this sequence folds into a monomolecular hairpin with non-canonical base pairing and B-DNA characteristics at concentrations below 0.9 mM. NMR studies at 0.05–0.5 mM indicate that the hairpin is likely folded-over into a compact structure with high dynamics. Crystallographic studies at 2.5 mM reveal an antiparallel self-complementary duplex with the same base pairing as in the hairpin, extended into an infinite polymer. The non-canonical base pairing includes a G–G intercalation sandwiched by sheared A–G base pairs, leading to a cross-strand four guanine stack, so called guanine zipper. The guanine zippers are spaced throughout the structure by A–T/T–A base pairs. Our findings lend further insight into recurring structural motifs associated with the HSat3 and their potential biological functions. Graphical Abstract Graphical Abstract
ISSN:0305-1048
1362-4962
DOI:10.1093/nar/gkae113