Conformational Dynamics of Strand Register Shifts in DNA G-Quadruplexes.
J Am Chem Soc
; 142(1): 264-273, 2020 01 08.
Article
in En
| MEDLINE
| ID: mdl-31815451
ABSTRACT
The complex folding energy landscape of DNA G-quadruplexes leads to numerous conformations for this functionally important class of noncanonical DNA structures. A new layer of conformational heterogeneity comes from sequences with different numbers of G-nucleotides in each of the DNA G-strands that form the four-stranded G-quartet core. The mechanisms by which G-quadruplexes transition from one folded conformation to another are currently unknown. To address this question, we studied two different G-quadruplexes, selecting a single conformation by blocking hydrogen bonding with photolabile protection groups. Upon irradiation, the block can be released and the kinetics of re-equilibration to the native conformational equilibrium can be determined by time-resolved NMR. We compared the NMR-derived refolding kinetics with data derived from thermal hysteresis folding kinetic experiments and found excellent agreement. The outlined methodological approach allows separation of K+-induced G-quadruplex formation and subsequent refolding and provides key insight into rate-limiting steps of G-quadruplex conformational dynamics.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
G-Quadruplexes
/
Nucleic Acid Conformation
Language:
En
Journal:
J Am Chem Soc
Year:
2020
Document type:
Article
Affiliation country: