Title :

Detection of single DNA mismatches by force spectroscopy in short DNA hairpins

Author(s) :

Landuzzi, F. [Auteur]
Viader-Godoy, X. [Auteur]
Universitat de Barcelona [UB]
Cleri, Fabrizio [Auteur]
Physique - IEMN [PHYSIQUE - IEMN]
Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 [IEMN]
Pastor, I. [Auteur]
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina [CIBER-BBN]
Universitat de Barcelona [UB]
Ritort, F. [Auteur correspondant]
Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina [CIBER-BBN]
Universitat de Barcelona [UB]

Journal title :

The Journal of Chemical Physics

Pages :

074204, 11 pages

Publisher :

American Institute of Physics

Publication date :

2020-02

ISSN :

0021-9606

English keyword(s) :

Free energy
Chemical thermodynamics
Optical trapping
Force spectroscopy
Probability theory
Steered molecular dynamics
Optical tweezer

HAL domain(s) :

Sciences de l'ingénieur [physics]

English abstract : [en]

Identification of defective DNA structures is a difficult task, since small differences in base-pair bonding are hidden in the local structural variability of a generally random base-pair sequence. Defects, such as base ...
Show more >Identification of defective DNA structures is a difficult task, since small differences in base-pair bonding are hidden in the local structural variability of a generally random base-pair sequence. Defects, such as base mismatches, missing bases, crosslinks, and so on, occur in DNA with high frequency and must be efficiently identified and repaired to avoid dire consequences such as genetic mutations. Here, we focus on the detection of base mismatches, which is local deviations from the ideal Watson-Crick pairing rule, which may typically originate from DNA replication process, foreign chemical attack, or ionizing radiation. Experimental detection of a mismatch defect demands the ability to measure slight deviations in the free energy and molecular structure. We introduce different mismatches in short DNA hairpins (10 or 20 base pairs plus a 4-base loop) sandwiched between dsDNA handles to be used in single-molecule force spectroscopy with optical tweezers. We perform both hopping and force-pulling experiments to measure the excess free energies and deduce the characteristic kinetic signatures of the mismatch from the force-distance curves. All-atom molecular dynamics simulations lend support to the detailed interpretation of the experimental data. Such measurements, at the lowest sensitivity limits of this experimental technique, demonstrate the capability of identifying the presence of mismatches in a random complementary dsDNA sequence and provide lower bounds for the ability to distinguish different structural defects.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Institut d'Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520

Source :

Harvested from HAL