BIOMAT Database Logo BIOMAT Database Logo

Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands. 1998

L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037, USA.

Sequence-specific DNA-binding small molecules that can permeate human cells potentially could regulate transcription of specific genes. Multiple cellular DNA-binding transcription factors are required by HIV type 1 for RNA synthesis. Two pyrrole-imidazole polyamides were designed to bind DNA sequences immediately adjacent to binding sites for the transcription factors Ets-1, lymphoid-enhancer binding factor 1, and TATA-box binding protein. These synthetic ligands specifically inhibit DNA-binding of each transcription factor and HIV type 1 transcription in cell-free assays. When used in combination, the polyamides inhibit virus replication by >99% in isolated human peripheral blood lymphocytes, with no detectable cell toxicity. The ability of small molecules to target predetermined DNA sequences located within RNA polymerase II promoters suggests a general approach for regulation of gene expression, as well as a mechanism for the inhibition of viral replication.

UI MeSH Term Description Entries
D008024 Ligands A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed) Ligand
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D009690 Nucleic Acid Conformation The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape. DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D009838 Oligodeoxyribonucleotides A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties. Oligodeoxynucleotide,Oligodeoxyribonucleotide,Oligodeoxynucleotides
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D012045 Regulatory Sequences, Nucleic Acid Nucleic acid sequences involved in regulating the expression of genes. Nucleic Acid Regulatory Sequences,Regulatory Regions, Nucleic Acid (Genetics),Region, Regulatory,Regions, Regulatory,Regulator Regions, Nucleic Acid,Regulatory Region,Regulatory Regions
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002474 Cell-Free System A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166) Cellfree System,Cell Free System,Cell-Free Systems,Cellfree Systems,System, Cell-Free,System, Cellfree,Systems, Cell-Free,Systems, Cellfree
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell

Related Publications

L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
Inhibition of RNA polymerase II transcription in human cell extracts by cisplatin DNA damage.
May 1999, Biochemistry,
L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
Regulation of RNA polymerase II transcription by sequence-specific DNA binding factors.
January 2004, Cell,
L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
Transcription of adenovirus 2 DNA by human RNA polymerase II in vitro.
January 1980, Molecular & general genetics : MGG,
L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
Transcription by RNA polymerase II in DNA-PK deficient scid mouse cells.
September 2000, Biochimica et biophysica acta,
L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
Direct inhibition of RNA polymerase II transcription by RECQL5.
August 2009, The Journal of biological chemistry,
L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
DNA wrapping in transcription initiation by RNA polymerase II.
January 1999, Biochemistry and cell biology = Biochimie et biologie cellulaire,
L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
Fast transcription rates of RNA polymerase II in human cells.
December 2011, EMBO reports,
L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
[Transcription of SV40 DNA I by RNA polymerase II from CVI cells in vitro].
February 1973, Archives internationales de physiologie et de biochimie,
L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
Transcription of methylated viral DNA by eukaryotic RNA polymerase II.
January 1989, Cell biophysics,
L A Dickinson, and R J Gulizia, and J W Trauger, and E E Baird, and D E Mosier, and J M Gottesfeld, and P B Dervan
Inhibition by flavonoids of RNA synthesis in permeable WI-38 cells and of transcription by RNA polymerase II.
December 1984, Biochemical pharmacology,
Copied contents to your clipboard!