DNA-DAMAGE BY ANTICANCER AGENTS RESOLVED AT THE NUCLEOTIDE LEVEL OF A SINGLE-COPY GENE - EVIDENCE FOR A NOVEL BINDING-SITE FOR CISPLATIN IN CELLS

被引：45

作者：

GRIMALDI, KA ^{[1
]}

MCADAM, SR ^{[1
]}

SOUHAMI, RL ^{[1
]}

HARTLEY, JA ^{[1
]}

机构：

[1] UCL, SCH MED, DEPT ONCOL, LONDON, ENGLAND

来源：

NUCLEIC ACIDS RESEARCH | 1994年 / 22卷 / 12期

关键词：

D O I：

10.1093/nar/22.12.2311

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A new PCR based technique has been developed to investigate the sequence selectivity of adduct formation by DNA damaging agents in a single copy gene in isolated genomic DNA or in drug treated cells. Single-strand ligation PCR (sslig-PCR) demonstrated that cisplatin and nitrogen mustards reacted with guanine in an N-ras fragment with varying sequence specificity similar to that observed previously in plasmid DNA. In cisplatin-treated cells sslig-PCR demonstrated all the adducts found in isolated DNA and with the same sequence selectivity showing a preference for GG and AG sites. However, in cells an additional site of DNA binding of cisplatin was observed at the two occurrences of the sequence 5'-TACT-3' on the transcribed and non-transcribed strands. This sequence is not a recognised target for cisplatin and represents a novel adduct formed in cells.

引用

页码：2311 / 2317

页数：7

共 35 条

[31] STRUCTURAL ASPECTS OF PLATINUM ANTICANCER DRUG-INTERACTIONS WITH DNA [J].