title: Molecular mechanisms and kinetics between DNA and DNA binding ligands.
abstract: Mechanical properties of single double-stranded DNA (dsDNA) in the presence of different binding ligands were analyzed in optical-tweezers experiments with subpiconewton force resolution. The binding of ligands to DNA changes the overall mechanic response of the dsDNA molecule. This fundamental property can be used for discrimination and identification of different binding modes and, furthermore, may be relevant for various processes like nucleosome packing or applications like cancer therapy. We compared the effects of the minor groove binder distamycin-A, a major groove binding alpha-helical peptide, the intercalators ethidium bromide, YO-1, and daunomycin as well as the bisintercalator YOYO-1 on lambda-DNA. Binding of molecules to the minor and major groove of dsDNA induces distinct changes in the molecular elasticity compared to the free dsDNA detectable as a shift of the overstretching transition to higher forces. Intercalating molecules affect the molecular mechanics by a complete disappearance of the B-S transition and an associated increase in molecular contour length. Significant force hysteresis effects occurring during stretching/relaxation cycles with velocities >10 nm/s for YOYO-1 and >1000 nm/s for daunomycin. These indicate structural changes in the timescale of minutes for the YOYO-DNA and of seconds for the daunomycin-DNA complexes, respectively.
authors.affiliation: Experimental Biophysics & Applied Nanosciences, Department of Physics, Bielefeld University, 33615 Bielefeld, Germany.
authors.forename: Andy
authors.initials: A
authors.lastname: Sischka
authors.forename: Katja
authors.initials: K
authors.lastname: Toensing
authors.forename: Rainer
authors.initials: R
authors.lastname: Eckel
authors.forename: Sven David
authors.initials: SD
authors.lastname: Wilking
authors.forename: Norbert
authors.initials: N
authors.lastname: Sewald
authors.forename: Robert
authors.initials: R
authors.lastname: Ros
authors.forename: Dario
authors.initials: D
authors.lastname: Anselmetti
mesh_terms: D001583:Benzoxazoles / Q000737:chemistry; D001703:Biophysics / Q000379:methods; D004247:DNA / Q000737:chemistry*; D003630:Daunorubicin / Q000737:chemistry / Q000494:pharmacology; D004214:Distamycins / Q000737:chemistry; D004996:Ethidium / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D007364:Intercalating Agents / Q000494:pharmacology; D007700:Kinetics; D007834:Lasers; D008024:Ligands; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011806:Quinolinium Compounds / Q000737:chemistry; D013997:Time Factors
chemical_list: D001583:Benzoxazoles; D004214:Distamycins; D005456:Fluorescent Dyes; D007364:Intercalating Agents; D008024:Ligands; D010455:Peptides; D011137:Polystyrenes; D011806:Quinolinium Compounds; C075296:1,1'-((4,4,7,7-tetramethyl)-4,7-diazaundecamethylene)bis-4-(3-methyl-2,3-dihydro(benzo-1,3-oxazole)-2-methylidene)quinolinium; C030000:stallimycin; D004247:DNA; D004996:Ethidium; D003630:Daunorubicin