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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number17
JournalGenes and Environment
Volume38
Issue number1
DOIs
Publication statusPublished - 2016 Jan 1
Externally publishedYes

Keywords

  • Deamination
  • Gene targeting
  • Mutagenesis
  • Mutagenic potential

ASJC Scopus subject areas

  • Social Psychology
  • Genetics
  • Environmental Science (miscellaneous)

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