Carbon-13 magnetic resonance spectra of 8-substituted purine nucleosides. Characteristic shifts for the syn conformation

Uesugi, Seiichi; Ikehara, Morio

doi:10.1021/ja00452a008

Cited by 170 publications

(107 citation statements)

References 4 publications

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“…At physiological pH, 8-oxoguanine has a carbonyl group at C8 and a proton at N7. Therefore, when 8-oxo-dG is paired with cytosine in the anti-conformation, a steric clash could occur between the C8-oxygen of 8-oxoguanine and O4Ј of the deoxyribose sugar (40,41). Comparing the structure of the normal duplex DNA and the DNA containing a single ribonucleotide, the sugar pucker conformation of an embedded ribonucleotide is locally changed to C3Ј-endo, whereas that of deoxyribonucleotides in the normal DNA is C2Ј-endo (42).…”

Section: Discussionmentioning

confidence: 99%

Impact of Ribonucleotide Backbone on Translesion Synthesis and Repair of 7,8-Dihydro-8-oxoguanine

Sassa

Çağlayan

Rodriguez

et al. 2016

Journal of Biological Chemistry

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Edited by Patrick SungNumerous ribonucleotides are incorporated into the genome during DNA replication. Oxidized ribonucleotides can also be erroneously incorporated into DNA. Embedded ribonucleotides destabilize the structure of DNA and retard DNA synthesis by DNA polymerases (pols), leading to genomic instability. Mammalian cells possess translesion DNA synthesis (TLS) pols that bypass DNA damage. The mechanism of TLS and repair of oxidized ribonucleotides remains to be elucidated. To address this, we analyzed the miscoding properties of the ribonucleotides riboguanosine (rG) and 7,8-dihydro-8-oxo-riboguanosine (8-oxo-rG) during TLS catalyzed by the human TLS pols and in vitro. The primer extension reaction catalyzed by human replicative pol ␣ was strongly blocked by 8-oxo-rG. pol inefficiently bypassed rG and 8-oxo-rG compared with dG and 7,8-dihydro-8-oxo-2-deoxyguanosine (8-oxo-dG), whereas pol easily bypassed the ribonucleotides. pol ␣ exclusively inserted dAMP opposite 8-oxo-rG. Interestingly, pol preferentially inserted dCMP opposite 8-oxo-rG, whereas the insertion of dAMP was favored opposite 8-oxo-dG. In addition, pol accurately bypassed 8-oxo-rG. Furthermore, we examined the activity of the base excision repair (BER) enzymes 8-oxoguanine DNA glycosylase (OGG1) and apurinic/apyrimidinic endonuclease 1 on the substrates, including rG and 8-oxorG. Both BER enzymes were completely inactive against 8-oxo-rG in DNA. However, OGG1 suppressed 8-oxo-rG excision by RNase H2, which is involved in the removal of ribonucleotides from DNA. These results suggest that the different sugar backbones between 8-oxo-rG and 8-oxo-dG alter the capacity of TLS and repair of 8-oxoguanine.

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Section: Discussionmentioning

confidence: 99%

Impact of Ribonucleotide Backbone on Translesion Synthesis and Repair of 7,8-Dihydro-8-oxoguanine

Sassa

Çağlayan

Rodriguez

et al. 2016

Journal of Biological Chemistry

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“…1A and Table 1). This could be due to a clash between the C8-oxygen of 8-oxoG and the phosphate backbone for the 8-oxoG in an anti-conformation (59). Based on structures of the TDG-DNA complex with an AP site or 5-carboxylcytosine (60,61), the side chain of Arg-275 inserts into the DNA minor groove to replace the flipped-out modified nucleotide.…”

Section: Discussionmentioning

confidence: 99%

Base Excision Repair of Tandem Modifications in a Methylated CpG Dinucleotide

Sassa

Çağlayan

Dyrkheeva

et al. 2014

Journal of Biological Chemistry

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Background: Base excision repair is an important pathway for cytosine demethylation at the CpG dinucleotide for epigenetic control. Results: A deaminated 5-methylcytosine (thymine) and an adjacent oxidized guanine (7,8-dihydro-8-oxoguanine) retard base excision repair of each lesion. Conclusion: Altered in-tandem CpG dinucleotide is a poor substrate for base excision repair. Significance: Oxidized guanine in a CpG dinucleotide interferes with active DNA demethylation.

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“…In addition, the Trp-28 and Trp-46 residues sandwich the adenine moiety, forming strong π-π stacking interactions. When we consider that 8-substituted purine nucleotides adopt the syn-conformation [39], the 8-oxo and 7-imino groups of both 8-OH-dGDP and 8-OH-dADP might be recognized by NUDT5 (possibly by Glu-47).…”

Section: Discussionmentioning

confidence: 99%

NUDT5 hydrolyzes oxidized deoxyribonucleoside diphosphates with broad substrate specificity

et al. 2009

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The human NUDT5 protein catalyzes the hydrolysis of 8-hydroxy-dGDP. To examine its substrate specificity, four oxidized deoxyribonucleotides (2-hydroxy-dADP, 8-hydroxy-dADP, 5-formyl-dUDP, and 5-hydroxy-dCDP) were incubated with the NUDT5 protein. Interestingly, all of the nucleotides, except for 5-hydroxy-dCDP, were hydrolyzed with various efficiencies. The kinetic parameters indicated that 8-hydroxy-dADP was hydrolyzed as efficiently as 8-hydroxy-dGDP.The hydrolyzing activities for their triphosphate counterparts were quite weak. These results suggest that the NUDT5 protein eliminates various oxidized deoxyribonucleoside diphosphates from the nucleotide pool and prevents their toxic effects.Keywords: NUDT5 / oxidized nucleotide / nucleotide pool sanitization / substrate recognition 3

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Carbon-13 magnetic resonance spectra of 8-substituted purine nucleosides. Characteristic shifts for the syn conformation

Cited by 170 publications

References 4 publications

Impact of Ribonucleotide Backbone on Translesion Synthesis and Repair of 7,8-Dihydro-8-oxoguanine

Impact of Ribonucleotide Backbone on Translesion Synthesis and Repair of 7,8-Dihydro-8-oxoguanine

Base Excision Repair of Tandem Modifications in a Methylated CpG Dinucleotide

NUDT5 hydrolyzes oxidized deoxyribonucleoside diphosphates with broad substrate specificity

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