title: Biophysical characterization of DNA binding from single molecule force measurements.
abstract: Single molecule force spectroscopy is a powerful method that uses the mechanical properties of DNA to explore DNA interactions. Here we describe how DNA stretching experiments quantitatively characterize the DNA binding of small molecules and proteins. Small molecules exhibit diverse DNA binding modes, including binding into the major and minor grooves and intercalation between base pairs of double-stranded DNA (dsDNA). Histones bind and package dsDNA, while other nuclear proteins such as high mobility group proteins bind to the backbone and bend dsDNA. Single-stranded DNA (ssDNA) binding proteins slide along dsDNA to locate and stabilize ssDNA during replication. Other proteins exhibit binding to both dsDNA and ssDNA. Nucleic acid chaperone proteins can switch rapidly between dsDNA and ssDNA binding modes, while DNA polymerases bind both forms of DNA with high affinity at distinct binding sites at the replication fork. Single molecule force measurements quantitatively characterize these DNA binding mechanisms, elucidating small molecule interactions and protein function.
authors.affiliation: Department of Physics, Northeastern University, 111 Dana Research Center, Boston, MA 02115, USA.
authors.forename: Kathy R
authors.initials: KR
authors.lastname: Chaurasiya
authors.forename: Thayaparan
authors.initials: T
authors.lastname: Paramanathan
authors.forename: Micah J
authors.initials: MJ
authors.lastname: McCauley
authors.forename: Mark C
authors.initials: MC
authors.lastname: Williams
mesh_terms: D001703:Biophysics / Q000379:methods*; D004247:DNA / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000737:chemistry / Q000378:metabolism; D018625:Microscopy, Atomic Force; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism
chemical_list: D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D018832:Molecular Chaperones; D004247:DNA; D004259:DNA-Directed DNA Polymerase