气候变化领域集成服务门户(CCPortal): Structural basis for recognition of distinct deaminated DNA lesions by endonuclease Q

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DOI	10.1073/pnas.2021120118
	Structural basis for recognition of distinct deaminated DNA lesions by endonuclease Q
	Shi K.; Moeller N.H.; Banerjee S.; McCann J.L.; Carpenter M.A.; Yin L.; Moorthy R.; Orellana K.; Harki D.A.; Harris R.S.; Aihara H.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	Spontaneous deamination of DNA cytosine and adenine into uracil and hypoxanthine, respectively, causes C to T and A to G transition mutations if left unrepaired. Endonuclease Q (EndoQ) initiates the repair of these premutagenic DNA lesions in prokaryotes by cleaving the phosphodiester backbone 5′ of either uracil or hypoxanthine bases or an apurinic/apyrimidinic (AP) lesion generated by the excision of these damaged bases. To understand how EndoQ achieves selectivity toward these structurally diverse substrates without cleaving undamaged DNA, we determined the crystal structures of Pyrococcus furiosus EndoQ bound to DNA substrates containing uracil, hypoxanthine, or an AP lesion. The structures show that substrate engagement by EndoQ depends both on a highly distorted conformation of the DNA backbone, in which the target nucleotide is extruded out of the helix, and direct hydrogen bonds with the deaminated bases. A concerted swing motion of the zinc-binding and C-terminal helical domains of EndoQ toward its catalytic domain allows the enzyme to clamp down on a sharply bent DNA substrate, shaping a deep active-site pocket that accommodates the extruded deaminated base. Within this pocket, uracil and hypoxanthine bases interact with distinct sets of amino acid residues, with positioning mediated by an essential magnesium ion. The EndoQ–DNA complex structures reveal a unique mode of damaged DNA recognition and provide mechanistic insights into the initial step of DNA damage repair by the alternative excision repair pathway. Furthermore, we demonstrate that the unique activity of EndoQ is useful for studying DNA deamination and repair in mammalian systems. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Deoxyinosine; Deoxyuridine; DNA damage repair; DNA deamination; Endonuclease
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180330
作者单位	Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, United States; Institute for Molecular Virology, University of Minnesota, Minneapolis, MN 55455, United States; Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, United States; Northeastern Collaborative Access Team, Cornell University, Advanced Photon Source, Lemont, IL 60439, United States; HHMI, University of Minnesota, Minneapolis, MN 55455, United States; Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, United States
推荐引用方式 GB/T 7714	Shi K.,Moeller N.H.,Banerjee S.,et al. Structural basis for recognition of distinct deaminated DNA lesions by endonuclease Q[J],2021,118(10).
APA	Shi K..,Moeller N.H..,Banerjee S..,McCann J.L..,Carpenter M.A..,...&Aihara H..(2021).Structural basis for recognition of distinct deaminated DNA lesions by endonuclease Q.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Shi K.,et al."Structural basis for recognition of distinct deaminated DNA lesions by endonuclease Q".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).