Structure and Dynamics of DNA and RNA Double Helices of CAG and GAC Trinucleotide Repeats.
Biophys J
; 113(1): 19-36, 2017 Jul 11.
Article
em En
| MEDLINE
| ID: mdl-28700917
ABSTRACT
CAG trinucleotide repeats are known to cause 10 late-onset progressive neurodegenerative disorders as the repeats expand beyond a threshold, whereas GAC repeats are associated with skeletal dysplasias and expand from the normal five to a maximum of seven repeats. The TR secondary structure is believed to play a role in CAG expansions. We have carried out free energy and molecular dynamics studies to determine the preferred conformations of the A-A noncanonical pairs in (CAG)n and (GAC)n trinucleotide repeats (n = 1, 4) and the consequent changes in the overall structure of the RNA and DNA duplexes. We find that the global free energy minimum corresponds to A-A pairs stacked inside the core of the helix with anti-anti conformations in RNA and (high-anti)-(high-anti) conformations in DNA. The next minimum corresponds to anti-syn conformations, whereas syn-syn conformations are higher in energy. Transition rates of the A-A conformations are higher for RNA than DNA. Mechanisms for these various transitions are identified. Additional structural and dynamical aspects of the helical conformations are explored, with a focus on contrasting CAG and GAC duplexes. The neutralizing ion distribution around the noncanonical pairs is described.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
DNA
/
RNA
/
Repetições de Trinucleotídeos
/
Conformação de Ácido Nucleico
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2017
Tipo de documento:
Article