Exp Mol Med.
2002 Nov;34(5):326-331.
Comparative binding of antitumor drugs to DNA containing the telomere repeat sequence
- Affiliations
-
- 1Department of Biochemostry, College of Medicine, Pochon CHA University, Kyungki-do, Korea. dcsuh@hanmail.net
- 2Department of Microbiology, College of Medicine, Pochon CHA University, Kyungki-do, Korea.
- 3Department of Microbiology & Genetic Engineering, University of Ulsan, Ulsan, Korea.
- 4Department of Biochemostry and Molecular Biology, Yonsei University, School of Medicine, Seoul, Korea.
- 5Department of Biological Science, Sungjyunkwan University, Suwon, Korea.
Abstract
- 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 mM bleomycin-Fe(III). These results imply that the stability of human telomere sequence is important in conjunction with the cancer treatment and aging process.
Keyword
MeSH Terms
-
Antineoplastic Agents/*metabolism
Bleomycin/metabolism/pharmacology
Circular Dichroism
Comparative Study
DNA/chemistry/drug effects/*metabolism
DNA Damage
Dactinomycin/metabolism
Doxorubicin/*analogs & derivatives/metabolism
Human
Nogalamycin/metabolism
Nucleic Acid Conformation
*Repetitive Sequences, Nucleic Acid
Telomere/drug effects/*genetics
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Different Phase of Telomere Shortening with Age in Peripheral Blood Mononuclear Cells
- Cooperative binding interaction of ethidium with allosteric DNA
- DNA Microarrays for Comparative Genomics: Identification of Conserved and Variable Sequences in Prokaryotic Genomes
- DNA Sequence Analysis on Internet
- Human FEN-1 can process the 5'-flap DNA of CTG/CAG triplet repeat derived from human genetic diseases by length and sequence dependent manner
