title: Spatial confinement induces hairpins in nicked circular DNA.
abstract: In living cells, DNA is highly confined in space with the help of condensing agents, DNA binding proteins and high levels of supercoiling. Due to challenges associated with experimentally studying DNA under confinement, little is known about the impact of spatial confinement on the local structure of the DNA. Here, we have used well characterized slits of different sizes to collect high resolution atomic force microscopy images of confined circular DNA with the aim of assessing the impact of the spatial confinement on global and local conformational properties of DNA. Our findings, supported by numerical simulations, indicate that confinement imposes a large mechanical stress on the DNA as evidenced by a pronounced anisotropy and tangent-tangent correlation function with respect to non-constrained DNA. For the strongest confinement we observed nanometer sized hairpins and interwound structures associated with the nicked sites in the DNA sequence. Based on these findings, we propose that spatial DNA confinement in vivo can promote the formation of localized defects at mechanically weak sites that could be co-opted for biological regulatory functions.
authors.affiliation: Laboratory of Physics of Living Matter, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Aleksandre
authors.initials: A
authors.lastname: Japaridze
authors.affiliation: Dipartimento di Fisica e Astronomia and Sezione INFN, Universita di Padova, Via Marzolo 8, 35131 Padova, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Orlandini
authors.affiliation: Laboratory of Physics of Living Matter, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Kathleen Beth
authors.initials: KB
authors.lastname: Smith
authors.affiliation: Laboratory of Physics of Living Matter, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Gmür
authors.affiliation: Consiglio Nazionale delle Ricerche (CNR), Istituto per lo Studio dei Materiali Nanostrutturati (ISMN), Via P.Gobetti 101, Bologna 40129, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Valle
authors.affiliation: SISSA - Scuola Internazionale Superiore di Studi Avanzati and CNR-IOM Democritos, Via Bonomea 265, 34136 Trieste, Italy.
authors.forename: Cristian
authors.initials: C
authors.lastname: Micheletti
authors.affiliation: Laboratory of Physics of Living Matter, EPFL, 1015 Lausanne, Switzerland.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Dietler
mesh_terms: D001483:Base Sequence / Q000235:genetics; D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure; D053904:DNA Breaks, Single-Stranded; D004270:DNA, Circular / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
chemical_list: D004270:DNA, Circular; D004268:DNA-Binding Proteins; D004247:DNA