Restriction-modification system with methyl-inhibited base excision and abasic-site cleavage activities
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Fukuyo-2015-Restriction-modifica.pdf
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Author(s)
Fukuyo, Masaki
Nakano, Toshiaki
Zhang, Yingbiao
Furuta, Yoshikazu
Ishikawa, Ken
Watanabe-Matsui, Miki
Yano, Hirokazu
Hamakawa, Takeshi
Ide, Hiroshi
Kobayashi, Ichizo
Date Issued
February 2015
Journal
Nucleic Acids Research
Publisher
Oxford University Press
Citation
Fukuyo, M., T. Nakano, Y. Zhang, Y. Furuta, K. Ishikawa, M. Watanabe-Matsui, H. Yano, T. Hamakawa, H. Ide, and I. Kobayashi. “Restriction-Modification System with Methyl-Inhibited Base Excision and Abasic-Site Cleavage Activities.” Nucleic Acids Research 43, no. 5 (February 19, 2015): 2841–2852.
Version
Final published version
Abstract
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 NaBH[subscript 4] 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.
MIT Department
Institute for Medical Engineering and Science
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DOI of Published Version
https://doi.org/10.1093/nar/gkv116
