Torsional sensing of small-molecule binding using magnetic tweezers.

ABSTRACT: DNA-binding small molecules are widespread in the cell and heavily used in biological applications. Here, we use magnetic tweezers, which control the force and torque applied to single DNAs, to study three small molecules: ethidium bromide (EtBr), a well-known intercalator; netropsin, a minor-groove binding anti-microbial drug; and topotecan, a clinically used anti-tumor drug. In the low-force limit in which biologically relevant torques can be accessed (<10 pN), we show that ethidium intercalation lengthens DNA ∼1.5-fold and decreases the persistence length, from which we extract binding constants. Using our control of supercoiling, we measure the decrease in DNA twist per intercalation to be 27.3±1° and demonstrate that ethidium binding delays the accumulation of torsional stress in DNA,

SUBMITTER: Lipfert J 

PROVIDER: S-EPMC2978369 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature