title: One-Dimensional Sliding of p53 Along DNA Is Accelerated in the Presence of Ca(2+) or Mg(2+) at Millimolar Concentrations.
abstract: One-dimensional (1D) sliding of the tumor suppressor p53 along DNA is an essential dynamics required for its efficient search for the binding sites in the genome. To address how the search process of p53 is affected by the changes in the concentration of Mg(2+) and Ca(2+) after the cell damages, we investigated its sliding dynamics at different concentrations of the divalent cations. The 1D sliding trajectories of p53 along the stretched DNA were measured by using single-molecule fluorescence microscopy. The averaged diffusion coefficient calculated from the mean square displacement of p53 on DNA increased significantly at the higher concentration of Mg(2+) or Ca(2+), indicating that the divalent cations accelerate the sliding likely by weakening the DNA-p53 interaction. In addition, two distributions were identified in the displacement of the observed trajectories of p53, demonstrating the presence of the fast and slow sliding modes having large and small diffusion coefficients, respectively. A coreless mutant of p53, in which the core domain was deleted, showed only a single mode whose diffusion coefficient is about twice that of the fast mode for the full-length p53. Thus, the two modes are likely the result of the tight and loose interactions between the core domain of p53 and DNA. These results demonstrated clearly that the 1D sliding dynamics of p53 is strongly dependent on the concentration of Mg(2+) and Ca(2+), which maintains the search distance of p53 along DNA in cells that lost homeostatic control of the divalent cations.
authors.affiliation: Institute for Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan; Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Agato
authors.initials: A
authors.lastname: Murata
authors.affiliation: Institute for Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan; Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Kashima
authors.affiliation: Institute for Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kanbayashi
authors.affiliation: Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai 980-8579, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nanatani
authors.affiliation: Institute for Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan; Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Igarashi
authors.affiliation: Institute for Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Okumura
authors.affiliation: Institute for Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Inaba
authors.affiliation: Department of Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Chuo-ku, Sapporo 060-8556, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tokino
authors.affiliation: Institute for Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan. Electronic address: st@tagen.tohoku.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Institute for Multidisciplinary Research for Advanced Materials, Tohoku University, Katahira 2-1-1, Aoba-ku, Sendai 980-8577, Japan. Electronic address: kamagata@tagen.tohoku.ac.jp.
authors.forename: Kiyoto
authors.initials: K
authors.lastname: Kamagata
mesh_terms: D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000737:chemistry*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D004058:Diffusion / Q000187:drug effects; D005454:Fluorescence Polarization; D006801:Humans; D008274:Magnesium / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D009690:Nucleic Acid Conformation; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004247:DNA; D008274:Magnesium; D002118:Calcium
keywords: DNA; divalent cation; p53; single-molecule; sliding