Comparative binding of antitumor drugs to DNA containing the telomere repeat sequence
| Autor: | Mi-Hyoung Lee, Hyo-Soon Joo, Yu-Kyoung Oh, Chung Kyoon Auh, Byungchan Ahn, Hye-Ja Kim, Dongchul Suh, Man-Wook Hur |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Telomerase
Guanine DNA damage Clinical Biochemistry Antineoplastic Agents Biochemistry DNA sequencing chemistry.chemical_compound Bleomycin Humans Molecular Biology Repetitive Sequences Nucleic Acid Chemistry Oligonucleotide Circular Dichroism DNA Telomere Molecular biology Doxorubicin Nogalamycin Nucleic acid Dactinomycin Molecular Medicine Nucleic Acid Conformation DNA Damage |
| Zdroj: | Experimentalmolecular medicine. 34(5) |
| ISSN: | 1226-3613 |
| Popis: | Telomeres are the ends of the linear chromosomes of eukaryotes and consist of tandem GT-rich repeats in telomere sequence i.e. 500-3000 repeats of 5'-TTAGGG-3' in human somatic cells, which are shortened gradually with age. The G-rich overhang of telomere sequence can adopt different intramolecular fold-backs and tetra-stranded DNA structures, in vitro, which inhibit telomerase activity. In this report, DNA binding agents to telomere sequence were studied novel therapeutic possibility to destabilize telomeric DNA sequences. Oligonucleotides containing the guanine repeats in human telomere sequence were synthesized and used for screening potential antitumor drugs. Telomeric DNA sequence was characterized using spectral measurements and CD spectroscopy. CD spectrum indicated that the double-stranded telomeric DNA is in a right-handed conformation. Polyacrylamide gel electrophoresis was performed for binding behaviors of antitumor compounds with telomeric DNA sequence. Drugs interacted with DNA sequence caused changes in the electrophoretic mobility and band intensity of the gels. Depending on the binding mode of the anticancer drugs, telomeric DNA sequence was differently recognized and the efficiency of cleavage of DNA varies in the bleomycin-treated samples under different conditions. DNA cleavage occurred at about 1% by the increments of 1 micromM bleomycin-Fe(III). These results imply that the stability of human telomere sequence is important in conjunction with the cancer treatment and aging process. |
| Databáze: | OpenAIRE |
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