Site specifically probing the unfolding process of human telomere i-motif DNA using vibrationally enhanced alkynyl stretch.
Phys Chem Chem Phys
; 26(5): 3857-3868, 2024 Jan 31.
Article
in En
| MEDLINE
| ID: mdl-38224126
ABSTRACT
The microscopic unfolding process of a cytosine-rich DNA forming i-motif by hemi-protonated base pairs is related to gene regulation. However, the detailed thermal unfolding mechanism and the protonation/deprotonation status of site-specific cytosine in DNA in a physiological environment are still obscure. To address this issue, a vibration-enhanced CîC probe tagged on 5'E terminal cytosine of human telomere i-motif DNA was examined using linear and nonlinear infrared (IR) spectroscopies and quantum-chemistry calculations. The CîC probe extended into the major groove of the i-motif was found using nonlinear IR results only to introduce a minor steric effect on both steady-state structure and local structure dynamics; however, its IR absorption profile effectively reports the cleavage of the hemi-protonated base pair of C1-C13 upon the unfolding with C1 remaining protonated. The temperature mid-point (Tm) of the local transition reported using the CîC tag was slightly lower than the Tm of global transition, and the enthalpy of the former exceeds 60% of the global transition. It is shown that the base-pair unraveling is noncooperative, with outer base pairs breaking first and being likely the rate limiting step. Our results offered an in-depth understanding of the macroscopic unfolding characteristics of the i-motif DNA and provided a nonlinear IR approach to monitoring the local structural transition and dynamics of DNA and its complexes.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA
/
Telomere
Limits:
Humans
Language:
En
Journal:
Phys Chem Chem Phys
Journal subject:
BIOFISICA
/
QUIMICA
Year:
2024
Type:
Article