Restriction-modification system with methyl-inhibited base excision and abasic-site cleavage activities

Masaki Fukuyo, Toshiaki Nakano, Yingbiao Zhang, Yoshikazu Furuta, Ken Ishikawa, Miki Watanabe-Matsui, Hirokazu Yano, Takeshi Hamakawa, Hiroshi Ide, Ichizo Kobayashi

研究成果: Article査読

5 被引用数 (Scopus)

抄録

The restriction-modification systems use epigenetic modification to distinguish between self and nonself DNA. A modification enzyme transfers a methyl group to a base in a specific DNA sequence while its cognate restriction enzyme introduces breaks in DNA lacking this methyl group. So far, all the restriction enzymes hydrolyze phosphodiester bonds linking the monomer units of DNA. We recently reported that a restriction enzyme (R.PabI) of the PabI superfamily with half-pipe fold has DNA glycosylase activity that excises an adenine base in the recognition sequence (5-GTAC). We now found a second activity in this enzyme: at the resulting apurinic/apyrimidinic (AP) (abasic) site (5'-GT#C, # = AP), its AP lyase activity generates an atypical strand break. Although the lyase activity is weak and lacks sequence specificity, its covalent DNA-R.PabI reaction intermediates can be trapped by NaBH4 reduction. The base excision is not coupled with the strand breakage and yet causes restriction because the restriction enzyme action can impair transformation ability of unmethylated DNA even in the absence of strand breaks in vitro. The base excision of R.PabI is inhibited by methylation of the target adenine base. These findings expand our understanding of genetic and epigenetic processes linking those in prokaryotes and eukaryotes.

本文言語English
ページ(範囲)2841-2852
ページ数12
ジャーナルNucleic acids research
43
5
DOI
出版ステータスPublished - 2015 3月 11

ASJC Scopus subject areas

  • 遺伝学

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