7CUK

Structure of a GG mismatch-containing duplex formed by G4C2 repeats

Summary for 7CUK

• Entry DOI: 10.2210/pdb7cuk/pdb
• Descriptor: DNA (11-mer) (1 entity in total)
• Functional Keywords: gg mismatched pair, g4c2 repeats, nmr- spectroscopy, dna duplex, dna
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 6748.42

Authors

Maity, A.,Chen, G.,Phan, A.T.,Winnerdy, F.R. (deposition date: 2020-08-23, release date: 2021-03-31, Last modification date: 2024-05-01)

Primary citation

Maity, A.,Winnerdy, F.R.,Chen, G.,Phan, A.T.
Duplexes Formed by G 4 C 2 Repeats Contain Alternate Slow- and Fast-Flipping G·G Base Pairs.
Biochemistry, 60:1097-1107, 2021

PubMed Abstract: Aberrant expansion of the hexanucleotide GGGGCC (or GC) repeat in the human gene is the most common genetic factor found behind amyotrophic lateral sclerosis and frontotemporal dementia. The hypothesized pathways, through which the repeat expansions contribute to the pathology, involve one or more secondary structural forms of the DNA and/or RNA sequences, such as G-quadruplexes, duplexes, and hairpins. Here, we study the structures of DNA and RNA duplexes formed by GC repeats, which contain G()·G() base pairs flanked by either G·C or C·G base pairs. We show that duplexes formed by GC repeats contain alternately two types of G·G pair contexts exhibiting different base flipping dynamics (∼100 ms vs ∼2 ms for DNA and ∼50 ms vs ∼20 ms for RNA at 10 °C, respectively) depending on the flanking bases, with the slow-flipping G·G pairs being flanked by a guanine at the 5'-end and the fast-flipping G·G pairs being flanked by a cytosine at the 5'-end. Our findings on the structures and dynamics of G·G base pairs in DNA and RNA duplexes formed by GC repeats provide a foundation for further studies of the functions and targeting of such biologically relevant motifs.

PubMed: 33750098
DOI: 10.1021/acs.biochem.0c00916

Experimental method

SOLUTION NMR