title: The interaction of cisplatin with a human telomeric DNA sequence containing seventeen tandem repeats.
abstract: The anti-tumour drug, cisplatin, preferentially forms adducts at G-rich DNA sequences. Telomeres are found at the ends of chromosomes and, in humans, contain the repeated DNA sequence (GGGTTA)(n) that is expected to be targeted by cisplatin. Using a plasmid clone with 17 tandem telomeric repeats, (GGGTTA)(17), the DNA sequence specificity of cisplatin was investigated utilising the linear amplification procedure that pin-pointed the precise sites of cisplatin adduct formation. This procedure used a fluorescently labelled primer and capillary electrophoresis with laser-induced fluorescence detection to determine the DNA sequence specificity of cisplatin. This technique provided a very accurate analysis of cisplatin-DNA adduct formation in a long telomeric repeat DNA sequence. The DNA sequence specificity of cisplatin in a long telomeric tandem repeat has not been previously reported. The results indicated that the 3'-end of the G-rich strand of the telomeric repeat was preferentially damaged by cisplatin and this suggests that the telomeric DNA repeat has an unusual conformation.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney NSW 2052, Australia.
authors.forename: Hanh T Q
authors.initials: HT
authors.lastname: Nguyen
authors.forename: Anne M
authors.initials: AM
authors.lastname: Galea
authors.forename: Vincent
authors.initials: V
authors.lastname: Murray
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D017931:DNA Primers; D006801:Humans; D020080:Tandem Repeat Sequences / Q000187:drug effects*; D016615:Telomere / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D017931:DNA Primers; D004247:DNA; D002945:Cisplatin