Torsional mechanics of DNA are regulated by small-molecule intercalation.
Summary of "Torsional mechanics of DNA are regulated by small-molecule intercalation."
Whether the bend and twist mechanics of DNA molecules are coupled is unclear. Here, we report the direct measurement of the resistive torque of single DNA molecules to study the effect of ethidium bromide (EtBr) intercalation and pulling force on DNA twist mechanics. DNA molecules were overwound and unwound using recently developed magnetic tweezers where the molecular resistive torque was obtained from Brownian angular fluctuations. The effect of EtBr intercalation on the twist stiffness was found to be significantly different from the effect on the bend persistence length. The twist stiffness of DNA was dramatically reduced at low intercalator concentration (<10 nM); however, it did not decrease further when the intercalator concentration was increased by 3 orders of magnitude. We also determined the dependence of EtBr intercalation on the torque applied to DNA. We propose a model for the elasticity of DNA base pairs with intercalated EtBr molecules to explain the abrupt decrease of twist stiffness at low EtBr concentration. These results indicate that the bend and twist stiffnesses of DNA are independent and can be differently affected by small-molecule binding.
Affiliation
Johns Hopkins Physical Science Oncology Center and Departments of Chemical and Biomolecular Engineering and Mechanical Engineering, The Johns Hopkins University, Baltimore, Maryland 21218, United States, and Department of Mechanical Engineering, Pontifici
Journal Details
This article was published in the following journal.
Name: The journal of physical chemistry. B
ISSN: 1520-5207
Pages: 16929-35
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21090816
- DOI: http://dx.doi.org/10.1021/jp107541q
Medical and Biotech [MESH] Definitions
Mechanics
The branch of physics which deals with the motions of material bodies, including kinematics, dynamics, and statics. When the laws of mechanics are applied to living structures, as to the locomotor system, it is referred to as BIOMECHANICS. (From Dorland, 28th ed)
Riboswitch
Part of a MESSENGER RNA molecule that undergoes a conformation change upon binding a specific metabolite or other small molecule thereby regulating the messenger RNA's transcription, post-transcriptional processing, transport, translation, or stability in response to varying levels of the metabolite or other small molecule.
Ligands
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Small Molecule Libraries
Large collections of small molecules (molecular weight about 600 or less), of similar or diverse nature which are used for high-throughput screening analysis of the gene function, protein interaction, cellular processing, biochemical pathways, or other chemical interactions.
Extracellular Signal-regulated Map Kinases
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
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