Miscoding Properties of 2′-Deoxyinosine, a Nitric Oxide-Derived DNA Adduct, during Translesion Synthesis Catalyzed by Human DNA Polymerases

Yasui, Masayoshi; Suenaga, Emi; Naoki, Katsuhiko; Masutani, Chikahide; Hanaoka, Fumio; Grúz, Petr; Shibutani, Shinya; Nohmi, Takehiko; Hayashi, Makoto; Honma, Masamitsu

doi:10.1016/j.jmb.2008.01.033

Cited by 55 publications

(63 citation statements)

References 49 publications

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“…Some unknown products were also observed (arrowheads in Fig. 2C) as previously reported (32,33). Using an 8-oxo-rG-modified template, pol preferentially incorporated the correct dCMP (47 Ϯ 5%) opposite 8-oxo-rG rather than dAMP (25 Ϯ 3%).…”

Section: Resultssupporting

confidence: 79%

“…To quantify base substitutions and deletions, the mobility of the reaction products was compared with those of Alexa 546-labeled 18-mer standard markers containing dC, dA, dG, or dT opposite the lesion and one-base (⌬ 1 ) or two-base (⌬ 2 ) deletions ( Fig. 2A) (33,52). Steady-state Kinetics Assay-Steady-state kinetic parameters for nucleotide insertion opposite dG, rG, 8-oxo-rG, or 8-oxo-dG and chain extension from the 3Ј terminus were determined at 25°C, using varying amounts of single dNTPs as described previously (33).…”

Section: Methodsmentioning

confidence: 99%

“…2A) (33,52). Steady-state Kinetics Assay-Steady-state kinetic parameters for nucleotide insertion opposite dG, rG, 8-oxo-rG, or 8-oxo-dG and chain extension from the 3Ј terminus were determined at 25°C, using varying amounts of single dNTPs as described previously (33). For nucleotide insertion, the reaction mixture contained 38-mer template (750 fmol) primed with Alexa 546-labeled 12-mer (500 fmol; 5Ј-AGAGGAAAGAAG).…”

Section: Methodsmentioning

confidence: 99%

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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: Resultssupporting

confidence: 79%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

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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“…Most forms of DNA damage, if inadequately repaired, can result in mutations, including pyrimidine dimers, oxidative and nitrosative damage [20e24, 59,60]. Furthermore, excessive levels of nitric oxide and its products inhibit DNA repair [41,61].…”

Section: Photocarcinogenesismentioning

confidence: 99%

Sunlight Protection by Vitamin D Compounds

et al. 2011

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“…Both DNA and RNA as well as unincorporated (deoxy)ribonucleotides are subjected to deamination (3). Inosine is read as guanosine (G) by cellular proteins, and in DNA this event is thus considered mutagenic (3,4). Consequences of adenosine deamination in RNA depend on which type and part of a transcript is deaminated and may result in altered coding, splicing, stability, and structure of an RNA or in intracellular relocalization (5).…”

mentioning

confidence: 99%

Regulation of Human Endonuclease V Activity and Relocalization to Cytoplasmic Stress Granules

Nawaz

Vik

Berges

et al. 2016

Journal of Biological Chemistry

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Endonuclease V (EndoV) is an enzyme with specificity for inosines in nucleic acids. Whereas the bacterial homologs are active on both DNA and RNA, the mammalian variants only cleave RNA, at least when assayed with recombinant proteins. Here we show that ectopically expressed, as well as endogenously expressed human (h)EndoV, share the same enzymatic properties as the recombinant protein and cleaves RNA with inosine but not DNA. In search for proteins interacting with hEndoV, polyadenylate-binding protein C1 (PABPC1) was identified. The association between PABPC1 and hEndoV is RNA dependent and furthermore, PABPC1 stimulates hEndoV activity and affinity for inosine-containing RNA. Upon cellular stress, PABPC1 relocates to cytoplasmic stress granules that are multimolecular aggregates of stalled translation initiation complexes formed to aid cell recovery. Arsenite, as well as other agents, triggered relocalization also of hEndoV to cytoplasmic stress granules. As inosines in RNA are highly abundant, hEndoV activity is likely regulated in cells to avoid aberrant cleavage of inosine-containing transcripts. Indeed, we find that hEndoV cleavage is inhibited by normal intracellular ATP concentrations. The ATP stores inside a cell do not overlay stress granules and we suggest that hEndoV is redistributed to stress granules as a strategy to create a local environment low in ATP to permit hEndoV activity.Deamination of adenosine (A) to inosine (I) is a reaction that occurs spontaneously in cells and is enhanced by exposure to nitrosative agents formed as a response to inflammation, infection, or from the environment (1, 2). Both DNA and RNA as well as unincorporated (deoxy)ribonucleotides are subjected to deamination (3). Inosine is read as guanosine (G) by cellular proteins, and in DNA this event is thus considered mutagenic (3, 4). Consequences of adenosine deamination in RNA depend on which type and part of a transcript is deaminated and may result in altered coding, splicing, stability, and structure of an RNA or in intracellular relocalization (5).In addition to arbitrary deamination events, inosine is also introduced in RNA by specific enzymes in a highly regulated manner to increase transcriptomic diversity (6). Responsible enzymes are the adenosine deaminases acting on RNA (ADARs) 2 that catalyze A to I editing on mRNA and non-coding (nc)RNA including long ncRNA, micro (mi)RNA and small interfering (si)RNA. A to I editing is abundant in higher eukaryotes and edited sites amount to more than 100 million and are spread over the majority of human genes (7). Defective editing is linked to various human diseases including neurological disorders, infections, and cancer (8 -11). Also some tRNAs undergo A to I editing at the anticodon wobble adenosine A 34 , a reaction that is catalyzed by adenosine deaminases acting on tRNA (ADATs) (12). ADATs are homologs to the ADARs and their editing is essential for protein synthesis (12, 13).Until recently, no enzymatic activity specific for inosine in RNA was known. However, endon...

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Miscoding Properties of 2′-Deoxyinosine, a Nitric Oxide-Derived DNA Adduct, during Translesion Synthesis Catalyzed by Human DNA Polymerases

Cited by 55 publications

References 49 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

Sunlight Protection by Vitamin D Compounds

Regulation of Human Endonuclease V Activity and Relocalization to Cytoplasmic Stress Granules

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