Crystal structure of the novel lesion-specific endonuclease PfuEndoQ from Pyrococcus furiosus. Issue 9 (12th April 2018)

• Record Type: Journal Article
• Authors: Miyazono, Ken-ichi; Ishino, Sonoko; Makita, Naruto; Ito, Tomoko; Ishino, Yoshizumi; Tanokura, Masaru
• Is Part Of: Nucleic acids research. Volume 46:Issue 9(2018)
• Page Start: 4807
• Page End: 4818
• Publication Date: 2018-04-12
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gky261
• Languages: English
• ISSNs: 0305-1048

Abstract

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 Zn 2+ -binding site and hydrolyses a phosphodiester bond using two Zn 2+ 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.