Unprecedented Hydrophobic Stabilizations from a Reverse Wobble T·T Mispair in DNA Minidumbbell
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AbstractMinidumbbell (MDB) is a newly found non-B DNA structure formed by short single-strand sequences. Up to now, three MDBs have been reported to form at neutral pH by sequences containing two repeats of TTTA, CCTG and CTTG. Among them, the thermodynamically less stable TTTA and CCTG MDBs have been proposed to be the structural intermediates that cause TTTA and CCTG repeat expansions during DNA replication in Staphylococcus aureus pathogen and myotonic dystrophy type 2 patients, respectively. Although the CTTG MDB has a melting temperature of at least 13 degrees C higher than those of the other two, no CTTG repeat expansion has ever been reported in any genomes. In this study, we successfully determined the solution structure of the CTTG MDB and observed for the first time the formation of a reverse wobble T center dot T mispair with two symmetric hydrogen bonds. More importantly, we identified unprecedented hydrophobic interactions between the two methyl groups of this T center dot T mispair and the four 2 '-methylene groups of their nearby loop-closing base pair residues. These stabilizations account for the substantial increase in the MDB thermodynamic stability which may govern the occurrence of repeat expansions. Communicated by Ramaswamy H. Sarma
All Author(s) ListGuo P, Lam SL
Journal nameJournal of Biomolecular Structure and Dynamics
Year2020
Month5
Volume Number38
Issue Number7
PublisherTaylor & Francis: STM, Behavioural Science and Public Health Titles
Pages1946 - 1953
ISSN0739-1102
eISSN1538-0254
LanguagesEnglish-United States

Last updated on 2021-21-09 at 00:13