Two sequential phosphates 3′ adjacent to the 8-oxoguanosine are crucial for lesion excision by E. coli Fpg protein and human 8-oxoguanine-DNA glycosylase

Rogacheva, Maria V.; Saparbaev, Murat; Afanasov, I. M.; Кузнецова, Светлана А.

doi:10.1016/j.biochi.2005.05.011

Cited by 6 publications

(11 citation statements)

References 30 publications

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“…An optimal DNA twisting plays an important part in lesion recognition by OGG1 [46], therefore OGG1 may not efficiently recognize 8-oxodG lesions close to dsDNA/ssDNA junctions where the degree of DNA twisting may be perturbed by ssDNA. In addition, a SSB, 3’ of the catalytic pocket hinders α-hOGG1 glycosylase activity [18, 19]. An 8-oxodG near a 3’ overhang completely lacks the complementary strand, and it is therefore possible that α-hOGG1 is compromised significantly in repairing oxidative base damages in the presence of a strand end near its active site pocket.…”

Section: Discussionmentioning

confidence: 99%

Factors that influence telomeric oxidative base damage and repair by DNA glycosylase OGG1

et al. 2011

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Telomeres are nucleoprotein complexes at the ends of linear chromosomes in eukaryotes, and are essential in preventing chromosome termini from being recognized as broken DNA ends. Telomere shortening has been linked to cellular senescence and human aging, with oxidative stress as a major contributing factor. 7, 8-dihydro-8-oxogaunine (8-oxodG) is one of the most abundant oxidative guanine lesions, and 8-oxoguanine DNA Glycosylase (OGG1) is involved in its removal. In this study, we examined if telomeric DNA is particularly susceptible to oxidative base damage and if telomere-specific factors affect the incision of oxidized guanines by OGG1. We demonstrated that telomeric TTAGGG repeats were more prone to oxidative base damage and repaired less efficiently than non-telomeric TG repeats in vivo. We also showed that the 8-oxodGincision activity of OGG1 is similar in telomeric and non-telomeric double-stranded substrates. In addition, telomere repeat binding factors TRF1 and TRF2 do not impair OGG1 incision activity. Yet, 8-oxodG in some telomere structures (e.g., fork-opening, 3'-overhang, and D-loop) were less effectively excised by OGG1, depending upon its position in these substrates. Collectively, our data indicate that the sequence context of telomere repeats and certain telomere configurations may contribute to telomere vulnerability to oxidative DNA damage processing.

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Section: Discussionmentioning

confidence: 99%

Factors that influence telomeric oxidative base damage and repair by DNA glycosylase OGG1

et al. 2011

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“…4–7,12–15 In addition to protein functional groups, the DNA backbone has been shown to play a role in base excision by several enzymes. 4,7,16–18 The best studied example is human uracil DNA glycosylase, in which DNA phosphates promote glycosidic bond cleavage by stabilizing the charge or conformation of the oxocarbenium intermediate. 4,7,16,17,19–21 …”

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confidence: 99%

Depurination of N7-Methylguanine by DNA Glycosylase AlkD Is Dependent on the DNA Backbone

2013

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DNA glycosylase AlkD excises N7-methylguanine (7mG) by a unique but unknown mechanism, in which the damaged nucleotide is positioned away from the protein and the phosphate backbone distorted. Here, we show by methylphosphonate substitution that a phosphate proximal to the lesion has a significant effect on the rate enhancement of 7mG depurination by the enzyme. Thus, instead of a conventional mechanism whereby protein side chains participate in N-glycosidic bond cleavage, AlkD remodels the DNA into an active site composed exclusively of DNA functional groups that provide the necessary chemistry to catalyze depurination.

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“…It is expected that cross-linking of the Fpg and hOgg1 proteins with DNA duplexes I-X occur in a specific manner because of the presence of the 8-oxoG residue (13,18). Consistent with this observation, oligonucleotide duplex XI bearing an SPI group in the same position as duplex IV, but having no 8-oxoG residue, failed to cross-link with Fpg and hOgg1 (Fig.…”

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confidence: 58%

“…Protein Preparation-The non-labeled wild-type and mutant Fpg and hOgg1 proteins were purified as previously described (17,18). In the present work, to facilitate MS data manipulation, the amino acid sequence of the Fpg protein was numbered beginning from P1, E2 .…”

Section: Methodsmentioning

confidence: 99%

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High Resolution Characterization of Formamidopyrimidine-DNA Glycosylase Interaction with Its Substrate by Chemical Cross-linking and Mass Spectrometry Using Substrate Analogs

Rogacheva

Ищенко

Saparbaev

et al. 2006

Journal of Biological Chemistry

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Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg) and human 8-oxoguanine-DNA glycosylase (hOgg1) initiate the base excision repair pathway for 7,8-dihydro-8-oxoguanine (8-oxoG) residues present in DNA. Recent structural and biochemical studies of Fpg-DNA and hOgg1-DNA complexes point to the existence of extensive interactions between phosphate groups and amino acids. However, the role of these contacts and their physiological relevance remains unclear. In the present study, we combined chemical cross-linking and electrospray ionization mass spectrometry (ESI/MS/MS) approaches to identify interacting residues in the Fpg-DNA and hOgg1-DNA complexes. The active centers of Fpg and hOgg1 were cross-linked with a series of reactive oligonucleotide duplexes containing both a single 8-oxoG residue and an O-ethyl-substituted pyrophosphate internucleotide (SPI) group at different positions in duplex DNA. The cross-linking efficiency reached 50% for Fpg and 30% for hOgg1. We have identified seven phosphate groups on both strands of the DNA duplex specifically interacting with nucleophilic amino acids in Fpg, and eight in hOgg1. MS/MS analysis of the purified proteolytic fragments suggests that lysine 56 of Fpg and lysine 249 of hOgg1 cross-link to the phosphate located 3 to the 8-oxoG residue. Site-specific mutagenesis analysis of Fpg binding to DNA substrate confirms the conclusions of our approach. Our results are consistent with crystallographic data on the Fpg-DNA complex and provide new data on the hOgg1-DNA interaction. The approach developed in this work provides a useful tool to study pro-and eukaryotic homologues of Fpg as well as other repair enzymes.Escherichia coli formamidopyrimidine-DNA glycosylase (Fpg) 2 (also known as MutM) and human 8-oxoguanine-DNA glycosylase (hOgg1) are DNA repair enzymes that catalyze the removal of 7,8-dihydro-8-oxoguanine (8-oxoG) residues from DNA (1-3). 8-OxoG is the major mutagenic base damage generated in DNA by reactive oxygen species produced in aerobic respiration and after cell injury or exposure to physical and chemical oxygen radical-forming agents (4). 8-OxoG is a miscoding lesion, because it pairs preferentially with adenine instead of cytosine and induces G⅐C 3 T⅐A transversions in vivo and in vitro (5, 6). Thus the Fpg and hOgg1 DNA glycosylases are important in prevention of the mutagenic effects of 8-oxoG residues present in DNA and maintenance of genome integrity. To date, most studies have focused on the interactions of Fpg and hOgg1 with oxidized bases, and little attention has been paid to contacts with phosphate groups in damaged DNA. However, it is evident that interactions of the DNA glycosylases with DNA phosphate groups are critical for the target search along DNA and base lesion recognition. It has been shown that the interaction of Fpg and hOgg1 with damaged DNA causes significant conformational changes in helix structure, such as partial denaturation, widening of the minor groove, sharp kinking of the DNA backbone at the lesion site, and flippi...

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Two sequential phosphates 3′ adjacent to the 8-oxoguanosine are crucial for lesion excision by E. coli Fpg protein and human 8-oxoguanine-DNA glycosylase

Cited by 6 publications

References 30 publications

Factors that influence telomeric oxidative base damage and repair by DNA glycosylase OGG1

Factors that influence telomeric oxidative base damage and repair by DNA glycosylase OGG1

Depurination of N7-Methylguanine by DNA Glycosylase AlkD Is Dependent on the DNA Backbone

High Resolution Characterization of Formamidopyrimidine-DNA Glycosylase Interaction with Its Substrate by Chemical Cross-linking and Mass Spectrometry Using Substrate Analogs

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