Crystal structure of the novel lesion-specific endonuclease PfuEndoQ from Pyrococcus furiosus

Ken ichi Miyazono, Sonoko Ishino, Naruto Makita, Tomoko Ito, Yoshizumi Ishino, Masaru Tanokura

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Because base deaminations, which are promoted by high temperature, ionizing radiation, aerobic respiration and nitrosative stress, produce mutations during replication, deaminated bases must be repaired quickly to maintain genome integrity. Recently, we identified a novel lesion-specific endonuclease, PfuEndoQ, from Pyrococcus furiosus, and PfuEndoQ may be involved in the DNA repair pathway in Thermococcales of Archaea. PfuEndoQ recognizes a deaminated base and cleaves the phosphodiester bond 5' of the lesion site. To elucidate the structural basis of the substrate recognition and DNA cleavage mechanisms of PfuEndoQ, we determined the structure of PfuEndoQ using X-ray crystallography. The PfuEndoQ structure and the accompanying biochemical data suggest that PfuEndoQ recognizes a deaminated base using a highly conserved pocket adjacent to a Zn2+-binding site and hydrolyses a phosphodiester bond using two Zn2+ ions. The PfuEndoQ-DNA complex is stabilized by a Zn-binding domain and a C-terminal helical domain, and the complex may recruit downstream proteins in the DNA repair pathway.

Original languageEnglish
Pages (from-to)4807-4818
Number of pages12
JournalNucleic acids research
Volume46
Issue number9
DOIs
Publication statusPublished - May 2018

All Science Journal Classification (ASJC) codes

  • Genetics

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