Mutagenic consequences of cytosine alterations site-specifically embedded in the human genome

Akira Sassa*, Yuki Kanemaru, Nagisa Kamoshita, Masamitsu Honma, Manabu Yasui

*この研究の対応する著者

研究成果: Article査読

12 被引用数 (Scopus)

抄録

Introduction: 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. Findings: 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.

本文言語English
論文番号17
ジャーナルGenes and Environment
38
1
DOI
出版ステータスPublished - 2016
外部発表はい

ASJC Scopus subject areas

  • 社会心理学
  • 遺伝学
  • 環境科学(その他)

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