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Comparative binding of antitumor drugs to DNA containing the telomere repeat sequence.

Authors
 Dongchul Suh  ;  Yu Kyoung Oh  ;  Byung Chan Ahn  ;  Man Wook Hur  ;  Hye Ja Kim  ;  Mi Hyoung Lee  ;  Hyo Soon Joo  ;  Chung Kyoon Auh 
Citation
 EXPERIMENTAL AND MOLECULAR MEDICINE, Vol.34(5) : 326-331, 2002 
Journal Title
 EXPERIMENTAL AND MOLECULAR MEDICINE 
ISSN
 1226-3613 
Issue Date
2002
MeSH
Antineoplastic Agents/metabolism* ; Bleomycin/metabolism ; Bleomycin/pharmacology ; Circular Dichroism ; DNA/chemistry ; DNA/drug effects ; DNA/metabolism* ; DNA Damage ; Dactinomycin/metabolism ; Doxorubicin/analogs & derivatives* ; Doxorubicin/metabolism ; Humans ; Nogalamycin/metabolism ; Nucleic Acid Conformation ; Repetitive Sequences, Nucleic Acid* ; Telomere/drug effects ; Telomere/genetics*
Keywords
antitumor drugs ; bleomycin ; DNA damage ; gel mobility ; telomere DNA
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 µM bleomycin-Fe(III). These results imply that the stability of human telomere sequence is important in conjunction with the cancer treatment and aging process.
Files in This Item:
T200207949.pdf Download
DOI
10.1038/emm.2002.54
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Hur, Man Wook(허만욱) ORCID logo https://orcid.org/0000-0002-3416-1334
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/144195
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