title: Mutagenic consequences of cytosine alterations site-specifically embedded in the human genome.
abstract: BACKGROUND
  Cytosine residues in CpG dinucleotides often undergo various types of modification, such as methylation, deamination, and halogenation. These types of modifications can be pro-mutagenic and can contribute to the formation of mutational hotspots in cells. To analyze mutations induced by DNA modifications in the human genome, we recently developed a system for tracing DNA adducts in targeted mutagenesis (TATAM). In this system, a modified/damaged base is site-specifically introduced into intron 4 of thymidine kinase genes in human lymphoblastoid cells. To further the understanding of the mutagenesis of cytosine modification, we directly introduced different types of altered cytosine residues into the genome and investigated their genomic consequences using the TATAM system.
  
  
  RESULTS
  In the genome, the pairing of thymine and 5-bromouracil with guanine, resulting from the deamination of 5-methylcytosine and 5-bromocytosine, respectively, was highly pro-mutagenic compared with the pairing of uracil with guanine, resulting from the deamination of cytosine residues.
  
  
  CONCLUSIONS
  The deamination of 5-methylcytosine and 5-bromocytosine rather than that of normal cytosine dramatically enhances the mutagenic potential in the human genome.
authors: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501 Japan.
authors: Akira
authors: A
authors: Sassa
authors: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501 Japan.|Present address: Division of Toxicology, Department of Pharmacology, Toxicology and Therapeutics, Showa University School of Pharmacy, Tokyo, 142-8555 Japan.
authors: Yuki
authors: Y
authors: Kanemaru
authors: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501 Japan.
authors: Nagisa
authors: N
authors: Kamoshita
authors: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501 Japan.
authors: Masamitsu
authors: M
authors: Honma
authors: Division of Genetics and Mutagenesis, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501 Japan.
authors: Manabu
authors: M
authors: Yasui
keywords: Deamination; Gene targeting; Mutagenesis; Mutagenic potential