Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A collection of 196 mutations induced in the SUP4-o gene of yeast by treatment with cis-diammine dichloroplatinum(II) (cis-DDP) was characterized by DNA sequencing. All possible types of base pair substitution were identified as well as deletions, insertions and double mutations. Base pair changes at G.C sites predominated and were distributed throughout the gene. The majority of substitutions occurred at 5'-GG-3' and 5'-GA-3' sequences, potential sites of cis-DDP adducts. However, mutations were also detected at a number of other DNA sequences where cis-DDP has been found to bind in vitro or form adducts in vivo including 5'-AA-3', 5'-AG-3', 5'-GNG-3' and 5'-AAA-3'. The site specificity of cis-DDP mutagenesis argues that some of these sequences are significant targets for the induction of mutation in vivo despite the fact that they were considered to be weak binding sites for cis-DDP in vitro. In addition, the distribution of the substitutions within the SUP4-o gene indicates that DNA sequence context influences cis-DDP mutagenesis in vivo. Finally, our results suggest that intrastrand cross-links formed by cis-DDP might facilitate the gain or loss of single base pairs by stabilizing strand misalignments that template these events.
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PMID:Analysis of mutations induced in the SUP4-o gene of Saccharomyces cerevisiae by cis-diammine dichloroplatinum(II). 218 17

Cisplatin was reacted with a 184-base-pair sequence, exon 3, of human HPRT DNA in vitro. The binding sites were mapped by a primer extension method with T4 DNA polymerase and radioactive dCTP. Binding sites of cisplatin were indicated by the lengths of synthesized polynucleotides as determined by gel electrophoresis. Neighboring GG dinucleotides were highly preferred sites of binding by cisplatin, while less binding was noted to GXG, GA, AAA, and GXA. Analysis by densitometry revealed a 5-fold difference in binding among the GG sequences. The relative binding to a GGG sequence exceeded that of a GGGGGG sequence, suggesting that the number of Gs in a run did not determine the relative binding.
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PMID:Binding of cisplatin to specific sequences of human DNA in vitro. 318 85