RRC ID 41685
Author Kamiya H, Tsuchiya H, Karino N, Ueno Y, Matsuda A, Harashima H.
Title Mutagenicity of 5-formylcytosine, an oxidation product of 5-methylcytosine, in DNA in mammalian cells.
Journal J Biochem
Abstract To examine the mutagenicity of 5-formylcytosine (5-fC), an oxidation product of 5-methylcytosine (5-mC), 5-fC was incorporated into predetermined sites of double-stranded shuttle vectors. The nucleotide sequences in which the modified base was incorporated were 5'-AFGCGT-3' and 5'-ACGFGT-3' (F represents 5-fC), the recognition site for the restriction enzyme MluI (5'-ACGCGT-3'). 5-fC was incorporated into the template strand of either the leading or lagging strand of DNA replication. The modified DNAs were transfected into simian COS-7 cells, and the DNAs replicated in the cells were recovered and analyzed after a second transfection into Escherichia coli. 5-fC weakly blocked DNA replication in mammalian cells. The 5-fC residues were mutagenic, with mutation frequencies in double-stranded vectors of 0.03-0.28%. The mutation spectrum of 5-fC was broad, and included targeted (5-fC-->G, 5-fC-->A, and 5-fC-->T) and untargeted mutations. These results suggest that the oxidation of 5-mC results in mutations at and around the modified sites.
Volume 132(4)
Pages 551-5
Published 2002-10-1
DOI 10.1093/oxfordjournals.jbchem.a003256
PMID 12359069
MeSH 5-Methylcytosine Animals Base Sequence COS Cells Chlorocebus aethiops Cytosine / analogs & derivatives* Cytosine / metabolism Cytosine / toxicity* DNA Damage* DNA Replication / drug effects Genetic Vectors / chemistry Genetic Vectors / genetics Mutagenesis, Site-Directed Mutagens / toxicity* Mutation* Oligodeoxyribonucleotides / chemistry Oxidation-Reduction Plasmids / genetics Templates, Genetic Transfection
IF 2.476
Times Cited 42
Human and Animal Cells