PMID: 19916941Nov 18, 2009Paper

Heavy metal ions affect the activity of DNA glycosylases of the fpg family

Biochemistry. Biokhimii︠a︡
I R GrinDmitry O Zharkov

Abstract

Prokaryotic enzymes formamidopyrimidine-DNA glycosylase (Fpg) and endonuclease VIII (Nei) and their eukaryotic homologs NEIL1, NEIL2, and NEIL3 define the Fpg family of DNA glycosylases, which initiate the process of repair of oxidized DNA bases. The repair of oxidative DNA lesions is known to be impaired in vivo in the presence of ions of some heavy metals. We have studied the effect of salts of several alkaline earth and transition metals on the activity of Fpg-family DNA glycosylases in the reaction of excision of 5,6-dihydrouracil, a typical DNA oxidation product. The reaction catalyzed by NEIL1 was characterized by values K(m) = 150 nM and k(cat) = 1.2 min(-1), which were in the range of these constants for excision of other damaged bases by this enzyme. NEIL1 was inhibited by Al3+, Ni2+, Co2+, Cd2+, Cu2+, Zn2+, and Fe2+ in Tris-HCl buffer and by Cd2+, Zn2+, Cu2+, and Fe2+ in potassium phosphate buffer. Fpg and Nei, the prokaryotic homologs of NEIL1, were inhibited by the same metal ions as NEIL1. The values of I(50) for NEIL1 inhibition were 7 microM for Cd2+, 16 microM for Zn2+, and 400 microM for Cu2+. The inhibition of NEIL1 by Cd2+, Zn2+, and Cu2+ was at least partly due to the formation of metal-DNA complexes. In the...Continue Reading

References

Jul 1, 1989·Biological Trace Element Research·A Hartwig, D Beyersmann
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K T TamaiD J Thiele
May 20, 1999·Annual Review of Pharmacology and Toxicology·C D KlaassenS Choudhuri
Jun 1, 2000·Journal of the American Society for Mass Spectrometry·R A RiegerC R Iden
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tapas K HazraSankar Mitra
Mar 26, 2002·The Journal of Biological Chemistry·Rotem GilboaGil Shoham
Apr 10, 2002·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Montserrat Soler-LópezJuan A Subirana
Apr 26, 2003·DNA Repair·Thomas A RosenquistArthur P Grollman
Aug 2, 2003·DNA Repair·Dmitry O ZharkovArthur P Grollman
Sep 25, 2003·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Shaunivan L LabiukJeremy S Lee
Nov 11, 2003·The Journal of Biological Chemistry·Elena I ZaikaDmitry O Zharkov
Jul 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Sylvie DoubliéSusan S Wallace
Jul 22, 2004·European Journal of Biochemistry·Holger BlessingAndrea Hartwig
Feb 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Vladimir VartanianR Stephen Lloyd
Feb 17, 2006·DNA Repair·Errol C Friedberg
Nov 1, 2007·Chemical Research in Toxicology·Konstantin Salnikow, Anatoly Zhitkovich
May 23, 2008·Archives of Toxicology·Detmar Beyersmann, Andrea Hartwig

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Citations

Mar 19, 2014·Analytica Chimica Acta·Chen LiHaizhen Zhu
May 17, 2011·Biochemistry. Biokhimii︠a︡·I R Grin, D O Zharkov
Nov 19, 2013·Biochemistry. Biokhimii︠a︡·L V GeningV Z Tarantul
May 19, 2018·Environmental Science. Processes & Impacts·Wen-Xiong WangNanyan Weng
Aug 29, 2018·Journal of Alzheimer's Disease : JAD·Sakae YumotoAkira Ishikawa
Jan 17, 2020·Metallomics : Integrated Biometal Science·Chao XingXiaofang Li
Jun 28, 2018·Molecular Neurobiology·Kowsar BavarsadAmirhossein Sahebkar

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