Synergistic Induction of the Senescence-Associated Genes by 5-Bromodeoxyuridine and AT-Binding Ligands in HeLa Cells
| Autor: | Toshikazu Suzuki, Michihiko Fujii, Hideki Ogino, Dai Ayusawa, Eriko Michishita |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Scaffold protein
Bromouracil Biology Antiviral Agents HeLa chemistry.chemical_compound Humans Nuclear Matrix RNA Messenger Gene Cellular Senescence Fluorescent Dyes Dose-Response Relationship Drug Distamycins Chromosome Mapping Nuclear Proteins Netropsin DNA Cell Biology Nuclear matrix biology.organism_classification AT Rich Sequence In vitro Thymine Chromatin Cell biology Eukaryotic Cells Bromodeoxyuridine Gene Expression Regulation Genes chemistry Biochemistry Bisbenzimidazole Cell Division HeLa Cells Protein Binding |
| Zdroj: | Experimental Cell Research. 276:174-184 |
| ISSN: | 0014-4827 |
| DOI: | 10.1006/excr.2002.5524 |
| Popis: | 5-Bromodeoxyuridine induces a senescence-like phenomenon in mammalian cells. This effect was dramatically potentiated by AT-binding ligands such as distamycin A, netropsin, and Hoechst 33258. The genes most remarkably affected by these ligands include the widely used senescence-associated genes and were located on or nearby Giemsa-dark bands of human chromosomes. We hypothesize that AT-rich scaffold/nuclear matrix attachment region sequences are involved in this phenomenon. In fact, upon substitution of thymine with 5-bromouracil, a rat S/MAR sequence reduced its degree of bending and became insensitive to cancellation of the bending by distamycin A. The S/MAR sequence containing 5-bromouracil also bound more tightly to nuclear scaffold proteins in vitro and this binding was not inhibited by distamycin A. Under the same conditions, the S/MAR sequence containing thymine easily dissociated from the nuclear scaffold proteins. Taken together, the synergistic induction of the genes may be explained not only by opening of condensed chromatin by distamycin A but also by increase in the binding of 5-bromouracil-containing S/MAR sequences to the nuclear scaffolds. |
| Databáze: | OpenAIRE |
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