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
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
Resource |
Human and Animal Cells |
|