Human polymorphic variants of the NEIL1 DNA glycosylase.

Human polymorphic variants of the NEIL1 DNA glycosylase. Research Abstract Details 

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Human polymorphic variants of the NEIL1 DNA glycosylase. Abstract Text:

Laura M Roy,Pawel Jaruga,Thomas G Wood,Amanda K McCullough,Miral Dizdaroglu,R Stephen Lloyd,

In mammalian cells, the repair of DNA bases that have been damaged by reactive oxygen species is primarily initiated by a series of DNA glycosylases that include OGG1, NTH1, NEIL1, and NEIL2. To explore the functional significance of NEIL1, we recently reported that neil1 knock-out and heterozygotic mice develop the majority of symptoms of metabolic syndrome (Vartanian, V., Lowell, B., Minko, I. G., Wood, T. G., Ceci, J. D., George, S., Ballinger, S. W., Corless, C. L., McCullough, A. K., and Lloyd, R. S. (2006) Proc. Natl. Acad. Sci. U. S. A. 103, 1864-1869). To determine whether this phenotype could be causally related to human disease susceptibility, we have characterized four polymorphic variants of human NEIL1. Although three of the variants (S82C, G83D, and D252N) retained near wild type levels of nicking activity on abasic (AP) site-containing DNA, G83D did not catalyze the wild type beta,delta-elimination reaction but primarily yielded the beta-elimination product. The AP nicking activity of the C136R variant was significantly reduced. Glycosylase nicking activities were measured on both thymine glycol-containing oligonucleotides and gamma-irradiated genomic DNA using gas chromatography/mass spectrometry. Two of the polymorphic variants (S82C and D252N) showed near wild type enzyme specificity and kinetics, whereas G83D was devoid of glycosylase activity. Although insufficient quantities of C136R could be obtained to carry out gas chromatography/mass spectrometry analyses, this variant was also devoid of the ability to incise thymine glycol-containing oligonucleotide, suggesting that it may also be glycosylase-deficient. Extrapolation of these data suggests that individuals who are heterozygous for these inactive variant neil1 alleles may be at increased risk for metabolic syndrome.

Human polymorphic variants of the NEIL1 DNA glycosylase. Publishing Authors By Initials

LM Roy,P Jaruga,TG Wood,AK McCullough,M Dizdaroglu,RS Lloyd,

For similar genetic phenomena: variation (genetics): polymorphism, genetic research abstracts see: genetic phenomena: variation (genetics): polymorphism, genetic research

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Human polymorphic variants of the NEIL1 DNA glycosylase. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of biological chemistry

VOLUME: 282

Page Numbers: 15790-8

Journal Abbreviation: J. Biol. Chem.

ISSN: 0021-9258

DAY: 26

MONTH: 03

YEAR: 2007

Human polymorphic variants of the NEIL1 DNA glycosylase. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985121

Human polymorphic variants of the NEIL1 DNA glycosylase. Keywords Mesh Terms:

KEYWORDS: Polymorphism, Genetic

MESH TERMS: chemistry

Chemical & Substance for Abstract: Human polymorphic variants of the NEIL1 DNA glycosylase. Information

Substance Name: NEIL2 protein, human

Registry Number: EC 4.2.99.18

Grant and Affiliation Information for Human polymorphic variants of the NEIL1 DNA glycosylase.

AFFILIATION: Center for Research on Occupational and Environmental Toxicology, Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon 97239-3098, USA.

Country: United States

AGENCY: United States NIEHS

GRANT: ES06676

ACRONYM: ES

MEDLINETA: J Biol Chem

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