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Michela Varra - One of the best experts on this subject based on the ideXlab platform.
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syntheses of 1 15n 2 Deoxyinosine 4 15n 2 deoxyaicar and 1 15n 2 deoxyguanosine
European Journal of Organic Chemistry, 1999Co-Authors: Bruno Catalanotti, Lorenzo De Napoli, Aldo Galeone, Luciano Mayol, Giorgia Oliviero, Gennaro Piccialli, Michela VarraAbstract:A high-yield synthesis of [1-15N]-2′-Deoxyinosine (5), [4-15N]-2′-deoxyAICAR (7), and [1-15N]-2′-deoxyguanosine (10) from 2′-Deoxyinosine (1) using relatively low expensive 15NH3 as 15N source is described. The method exploits 2-C reactivity of 2′-Deoxyinosine (1) to obtain its 15N-labelled counterpart, through [1-15N]-2′-Deoxyinosine (5), and successively, [4-15N]-2′-deoxyAICAR (7). [1-15N]-2′-Deoxyguanosine (10) can be prepared as well, through an improved cyclization procedure. No protection of sugar hydroxyl groups is required at any stage.
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Syntheses of [1-15N]-2′-Deoxyinosine, [4-15N]-2′-DeoxyAICAR, and [1-15N]-2′-Deoxyguanosine
European Journal of Organic Chemistry, 1999Co-Authors: Bruno Catalanotti, Lorenzo De Napoli, Aldo Galeone, Luciano Mayol, Giorgia Oliviero, Gennaro Piccialli, Michela VarraAbstract:A high-yield synthesis of [1-15N]-2′-Deoxyinosine (5), [4-15N]-2′-deoxyAICAR (7), and [1-15N]-2′-deoxyguanosine (10) from 2′-Deoxyinosine (1) using relatively low expensive 15NH3 as 15N source is described. The method exploits 2-C reactivity of 2′-Deoxyinosine (1) to obtain its 15N-labelled counterpart, through [1-15N]-2′-Deoxyinosine (5), and successively, [4-15N]-2′-deoxyAICAR (7). [1-15N]-2′-Deoxyguanosine (10) can be prepared as well, through an improved cyclization procedure. No protection of sugar hydroxyl groups is required at any stage.
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1-Substituted 2′-Deoxyinosine analogues
Journal of the Chemical Society Perkin Transactions 1, 1997Co-Authors: Lorenzo De Napoli, Gennaro Piccialli, Anna Messere, Daniela Montesarchio, Michela VarraAbstract:The base 2-carbon of 2′,3′-di-O-acetyl-2′-Deoxyinosine is strongly activated towards nucleophilic attack when either the 4-nitrophenyl or 2,4-dinitrophenyl group is attached to its N-1 position (product 1 or 2). 1-(ω-Aminoalkyl)- and 1-(ω-hydroxyalkyl)-2′-Deoxyinosine derivatives 5, 8–10 have been efficiently synthesized by a rearrangement of the purine ring upon treatment of compound 1 or 2 with the appropriate α,ω-diamine or α,ω-hydroxyamine. Moreover 1-amino-2′-Deoxyinosine 11 and 1-hydroxy-2′-Deoxyinosine 13 have been easily prepared in high yields by reaction of substrate 1 or 2, respectively, with hydrazine or hydroxylamine.
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1 substituted 2 Deoxyinosine analogues
Journal of The Chemical Society-perkin Transactions 1, 1997Co-Authors: Lorenzo De Napoli, Gennaro Piccialli, Anna Messere, Daniela Montesarchio, Michela VarraAbstract:The base 2-carbon of 2′,3′-di-O-acetyl-2′-Deoxyinosine is strongly activated towards nucleophilic attack when either the 4-nitrophenyl or 2,4-dinitrophenyl group is attached to its N-1 position (product 1 or 2). 1-(ω-Aminoalkyl)- and 1-(ω-hydroxyalkyl)-2′-Deoxyinosine derivatives 5, 8–10 have been efficiently synthesized by a rearrangement of the purine ring upon treatment of compound 1 or 2 with the appropriate α,ω-diamine or α,ω-hydroxyamine. Moreover 1-amino-2′-Deoxyinosine 11 and 1-hydroxy-2′-Deoxyinosine 13 have been easily prepared in high yields by reaction of substrate 1 or 2, respectively, with hydrazine or hydroxylamine.
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Reaction of 3′,5′-di-O-acetyl-2′-Deoxyinosine with the chlorinating agent PPh3–CCl4: synthesis of the 6-chloroderivative and of a new base linked dimer, useful intermediate to 15N-1-labelled 2′-Deoxyinosine
J. Chem. Soc. Perkin Trans. 1, 1994Co-Authors: L. De Napoli, Gennaro Piccialli, Anna Messere, Daniela Montesarchio, Ciro Santacroce, Michela VarraAbstract:Treatment of 3′,5′-di-O-acetyl-2′-Deoxyinosine 1 with PPh3–CCl4 in the presence of catalytic 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) afforded 6-chloro-9-(2′-deoxy-3′,5′di-O-acetyl-β-D-ribofuranosyl)purine 3. Use of an excess of DBU gave the new dimeric bipurine 5(90%) which proved to be a useful intermediate for obtaining, in one step, [15N-1]-2′-Deoxyinosine.
Y. W. Kow - One of the best experts on this subject based on the ideXlab platform.
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Human endonuclease V as a repair enzyme for DNA deamination.
Mutation research, 2012Co-Authors: Maria Alford-zappala, Y. W. Kow, Richard P Cunningham, Weiguo CaoAbstract:The human endonuclease V gene is located in chromosome 17q25.3 and encodes a 282 amino acid protein that shares about 30% sequence identity with bacterial endonuclease V. This study reports biochemical properties of human endonuclease V with respect to repair of deaminated base lesions. Using soluble proteins fused to thioredoxin at the N-terminus, we determined repair activities of human endonuclease V on Deoxyinosine (I)-, deoxyxanthosine (X)-, deoxyoxanosine (O)- and deoxyuridine (U)-containing DNA. Human endonuclease V is most active with Deoxyinosine-containing DNA but with minor activity on deoxyxanthosine-containing DNA. Endonuclease activities on deoxyuridine and deoxyoxanosine were not detected. The endonuclease activity on Deoxyinosine-containing DNA follows the order of single-stranded I>G/I>T/I>A/I>C/I. The preference of the catalytic activity correlates with the binding affinity of these Deoxyinosine-containing DNAs. Mg(2+) and to a much less extent, Mn(2+), Ni(2+), Co(2+) can support the endonuclease activity. Introduction of human endonuclease V into Escherichia coli cells deficient in nfi, mug and ung genes caused three-fold reduction in mutation frequency. This is the first report of deaminated base repair activity for human endonuclease V. The relationship between the endonuclease activity and deaminated deoxyadenosine (Deoxyinosine) repair is discussed.
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a Deoxyinosine specific endonuclease from hyperthermophile archaeoglobus fulgidus a homolog of escherichia coli endonuclease v
Mutation Research-dna Repair, 2000Co-Authors: Jiang Liu, Hong Qing, Y. W. KowAbstract:Abstract Deoxyadenosine undergoes spontaneous deamination to Deoxyinosine in DNA. Based on amino acids sequence homology, putative homologs of endonuclease V were identified in several organisms including archaebacteria, eubacteria as well as eukaryotes. The translated amino acid sequence of the Archaeoglobus fulgidus nfi gene shows 39% identity and 55% similarity to the E. coli nfi gene. A. fulgidus endonuclease V was cloned and expressed in E. coli as a C-terminal hexa–histidine fusion protein. The C-terminal fusion protein was purified to apparent homogeneity by a combination of Ni++ affinity and MonoS cation exchange liquid chromatography. The purified C-terminal fusion protein has a molecular weight of about 25 kDa and showed endonuclease activity towards DNA containing Deoxyinosine. A. fulgidus endonuclease V has an absolute requirement for Mg2+ and an optimum reaction temperature at 85°C. However, in contrast to E. coli endonuclease V, which has a wide substrate spectrum, endonuclease V from A. fulgidus recognized only Deoxyinosine. These data suggest that the Deoxyinosine cleavage activity is a primordial activity of endonuclease V and that multiple enzymatic activities of E. coli endonuclease V were acquired later during evolution.
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Further Characterization of Escherichia coliEndonuclease V MECHANISM OF RECOGNITION FOR Deoxyinosine, DEOXYURIDINE, AND BASE MISMATCHES IN DNA
The Journal of biological chemistry, 1997Co-Authors: Min Yao, Y. W. KowAbstract:Abstract Endonuclease V from Escherichia colihas a wide substrate spectrum. In addition to Deoxyinosine-containing DNA, the enzyme cleaves DNA containing urea residues, AP sites, base mismatches, insertion/deletion mismatches, flaps, and pseudo-Y structures. The gene coding for the enzyme was identified to beorf 225 or nfi(e n donuclease fi ve). Using enzyme purified from an overproducing strain, the Deoxyinosine- and mismatch-specific activities of endonuclease V was found to have different divalent metal requirements. The affinity of the enzyme is greater than 20-fold higher for DNA containing Deoxyinosine than deoxynebularine or base mismatches. Under optimal cleavage conditions, endonuclease V forms two stable complexes with DNA containing Deoxyinosine, but not with DNA containing base mismatches or deoxynebularine, suggesting that the 6-keto group of hypoxanthine in DNA is critical for stable interactions with the protein. The enzyme recognizes deoxyuridine in DNA but exhibits a much lower affinity to DNA containing deoxyuridine compared with DNA containing Deoxyinosine. Interestingly, deoxyuridine-specific endonuclease activity of endonuclease V has a divalent metal requirement similar to the mismatch activity. A model for the mechanism of substrate recognition is proposed to explain these different activities.
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Cleavage of Insertion/Deletion Mismatches, Flap and Pseudo-Y DNA Structures by Deoxyinosine 3′-Endonuclease from Escherichia coli
The Journal of biological chemistry, 1996Co-Authors: Min Yao, Y. W. KowAbstract:Abstract Deoxyinosine 3′-endonuclease, an Escherichia coli repair enzyme that recognizes and cleaves DNA containing Deoxyinosine and base mismatches, can cleave heteroduplexes containing a hairpin or unpaired loop. These DNA structures, referred to as insertion/deletion mismatches (IDM), are abnormal intermediate structures generated during replication of repetitive DNA sequences. In addition, the enzyme also cleaved the 5′-single-stranded tails of flap and pseudo-Y DNA structures, suggesting that Deoxyinosine 3′-endonuclease is a bacterial functional homologue of human FEN1 and yeast RTH1 nucleases. These biochemical properties suggest that Deoxyinosine 3′-endonuclease might be important in the repair of IDM structures generated in lagging strand during DNA replication.
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cleavage of insertion deletion mismatches flap and pseudo y dna structures by Deoxyinosine 3 endonuclease from escherichia coli
Journal of Biological Chemistry, 1996Co-Authors: Min Yao, Y. W. KowAbstract:Abstract Deoxyinosine 3′-endonuclease, an Escherichia coli repair enzyme that recognizes and cleaves DNA containing Deoxyinosine and base mismatches, can cleave heteroduplexes containing a hairpin or unpaired loop. These DNA structures, referred to as insertion/deletion mismatches (IDM), are abnormal intermediate structures generated during replication of repetitive DNA sequences. In addition, the enzyme also cleaved the 5′-single-stranded tails of flap and pseudo-Y DNA structures, suggesting that Deoxyinosine 3′-endonuclease is a bacterial functional homologue of human FEN1 and yeast RTH1 nucleases. These biochemical properties suggest that Deoxyinosine 3′-endonuclease might be important in the repair of IDM structures generated in lagging strand during DNA replication.
Mahesh K Lakshman - One of the best experts on this subject based on the ideXlab platform.
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O6-(benzotriazol-1-yl)inosine derivatives for C6 modification of purine nucleosides.
Current protocols in nucleic acid chemistry, 2009Co-Authors: Suyeal Bae, Surendra Chaturvedi, Mahesh K LakshmanAbstract:A new class of reactive nucleosides, O(6)-(benzotriazol-1-yl) derivatives of inosine and 2'-Deoxyinosine, have been developed via reaction of silyl-protected or unprotected inosine and 2'-Deoxyinosine with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). Alternatively, the silyl-protected O(6)-(benzotriazol-1-yl) derivatives can be synthesized via reaction of protected inosine and 2'-Deoxyinosine with triphenylphosphine/iodine/1-hydroxybenzotriazole. These new O(6)-(benzotriazol-1-yl) inosine derivatives are excellent reagents for the synthesis of other nucleoside analogues via S(N)Ar reaction with a range of nucleophiles.
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Current Protocols in Nucleic Acid Chemistry - O6-(benzotriazol-1-yl)inosine derivatives for C6 modification of purine nucleosides.
Current Protocols in Nucleic Acid Chemistry, 2009Co-Authors: Suyeal Bae, Surendra Chaturvedi, Mahesh K LakshmanAbstract:A new class of reactive nucleosides, O6-(benzotriazol-1-yl) derivatives of inosine and 2′-Deoxyinosine, have been developed via reaction of silyl-protected or unprotected inosine and 2′-Deoxyinosine with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). Alternatively, the silyl-protected O6-(benzotriazol-1-yl) derivatives can be synthesized via reaction of protected inosine and 2′-Deoxyinosine with triphenylphosphine/iodine/1-hydroxybenzotriazole. These new O6-(benzotriazol-1-yl) inosine derivatives are excellent reagents for the synthesis of other nucleoside analogues via SNAr reaction with a range of nucleophiles. Curr. Protoc. Nucleic Acid Chem. 36:1.22.1-1.22.23. © 2009 by John Wiley & Sons, Inc. Keywords: inosine; 2′-Deoxyinosine; BOP; reactive nucleosides; convertible nucleosides; benzotriazolyl
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o6 benzotriazol 1 yl inosine derivatives easily synthesized reactive nucleosides
Journal of the American Chemical Society, 2007Co-Authors: Mahesh K LakshmanAbstract:A novel class of O6-(benzotriazol-1-yl)inosine as well as the corresponding 2‘-deoxy derivatives can be conveniently prepared by a reaction between sugar-protected or -unprotected inosine or 2‘-Deoxyinosine nucleosides and 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP). The reaction appears to proceed via a nucleoside phosphonium salt, and in the absence of any additional nucleophile, the released 1-hydroxybenzotriazole undergoes reaction with the formed phosphonium salt leading to the requisite O6-(benzotriazol-1-yl)inosine or 2‘-Deoxyinosine derivatives. Isolation and characterization of the phosphonium salt as well as analysis by 31P{1H} NMR appear to be consistent with this reaction pathway. The resulting O6-(benzotriazol-1-yl)inosine derivatives are effective as electrophilic nucleosides, undergoing facile reactions with a variety of nucleophiles such as alcohols, phenols, amines, and a thiol. Unusual and challenging nucleoside derivatives such as an aryl-bridged dim...
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Synthesis and reactions of 2-chloro- and 2-tosyloxy-2'-Deoxyinosine derivatives.
The Journal of organic chemistry, 2005Co-Authors: Narender Pottabathini, Suyeal Bae, Padmanava Pradhan, Hoh-gyu Hahn, Heduck Mah, Mahesh K LakshmanAbstract:Convenient syntheses of 2-chloro- and 2-tosyloxy-2'-Deoxyinosine as their tert-butyldimethylsilyl ethers are described. Both compounds can be synthesized via a common route and rely on commercially available 2'-deoxyguanosine. The present method leading to the chloro nucleoside is operationally simpler compared to previously reported glycosylation techniques where isomeric products were obtained. Both electrophilic nucleosides can be used for the preparation of N-substituted 2'-deoxyguanosine analogues via displacement of the leaving groups, and a comparison of their reactivities shows the chloro analogue to be superior. Interestingly, a Pd catalyst-mediated, two-step, one-pot conversion of an allyl-protected chloro nucleoside intermediate to the final modified 2'-deoxyguanosine derivatives is also feasible. On the basis of these observations, initial assessments of Pd-catalyzed aryl amination as well as a C-C cross-coupling have also been performed with the chloro and tosyloxy nucleoside substrates. Results indicate a potentially high synthetic utility of 2-chloro-2'-Deoxyinosine and in many instances this derivative can supplant the bromo and fluoro analogues that are more cumbersome to prepare or are not readily available.
Ramon Eritja - One of the best experts on this subject based on the ideXlab platform.
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Studies on the Synthesis of Oligonucleotides Containing Photoreactive Nucleosides: 2-Azido-2′-Deoxyinosine and 8-Azido-2′-Deoxyadenosine
Biological chemistry, 1998Co-Authors: Carmen Fabrega, R. Guimil Garcia, Antonio R. Díaz, Ramon EritjaAbstract:Oligonucleotides containing the photoreactive nucleosides 2-azido-2'-Deoxyinosine and 8-azido-2'-deoxyadenosine have been prepared using protected 2-fluoro-2'-Deoxyinosine and 8-bromo-2'-deoxyadenosine phosphoramidites. After the assembly of the oligonucleotides, the nucleoside derivatives are converted to the corresponding azido derivatives by treatment with lithium azide in dry DMF. Deprotection of oligonucleotides carrying these azidonucleosides is performed with concentrated ammonia at room temperature.
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studies on the synthesis of oligonucleotides containing photoreactive nucleosides 2 azido 2 Deoxyinosine and 8 azido 2 deoxyadenosine
Biological Chemistry, 1998Co-Authors: Carmen Fabrega, Antonio R. Díaz, Guimil R Garcia, Ramon EritjaAbstract:Oligonucleotides containing the photoreactive nucleosides 2-azido-2'-Deoxyinosine and 8-azido-2'-deoxyadenosine have been prepared using protected 2-fluoro-2'-Deoxyinosine and 8-bromo-2'-deoxyadenosine phosphoramidites. After the assembly of the oligonucleotides, the nucleoside derivatives are converted to the corresponding azido derivatives by treatment with lithium azide in dry DMF. Deprotection of oligonucleotides carrying these azidonucleosides is performed with concentrated ammonia at room temperature.
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synthesis of oligodeoxynucleotides containing 2 substituted guanine derivatives using 2 fluoro 2 Deoxyinosine as common nucleoside precursor
Nucleosides Nucleotides & Nucleic Acids, 1997Co-Authors: Antonio R. Díaz, Ramon Eritja, Ramon Güimil GarcíaAbstract:Abstract Oligonucleotides containing 2-substituted guanine derivatives with double-helix stabilizing molecules such as spermine, spermidine and propylimidazole have been prepared using protected 2-fluoro-2′-Deoxyinosine phosphoramidite and two different protective strategies: the p-nitrophenylethyl (NPE) and the t-butylphenoxyacetyl groups. Melting studies show a large increase on the melting temperatures of duplexes containing these 2-substituted guanine derivatives.
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Synthesis of Oligodeoxynucleotides Containing 2-Substituted Guanine Derivatives Using 2-Fluoro-2′-Deoxyinosine as Common Nucleoside Precursor
Nucleosides and Nucleotides, 1997Co-Authors: Antonio R. Díaz, Ramon Eritja, Ramon Güimil GarcíaAbstract:Abstract Oligonucleotides containing 2-substituted guanine derivatives with double-helix stabilizing molecules such as spermine, spermidine and propylimidazole have been prepared using protected 2-fluoro-2′-Deoxyinosine phosphoramidite and two different protective strategies: the p-nitrophenylethyl (NPE) and the t-butylphenoxyacetyl groups. Melting studies show a large increase on the melting temperatures of duplexes containing these 2-substituted guanine derivatives.
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preparation of oligonucleotides containing daica using an unexpected side reaction observed on a protected derivative of 2 aza 2 Deoxyinosine
Tetrahedron, 1991Co-Authors: Dolors Fernandezforner, Ramon Eritja, F. Bardella, Xavier Solans, Ernest Giralt, Catalina Ruizperez, Enrique PedrosoAbstract:Abstract Attempts of synthesis of oligonucleotides containing 2-aza-2′-Deoxyinosine protected with the N,N-diphenylcarbamoyl group are described. An unexpected behaviour of the protected nucleoside can be used for the introduction of dAICA in synthetic oligonucleotides.
Yoshizumi Ishino - One of the best experts on this subject based on the ideXlab platform.
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A novel endonuclease that may be responsible for damaged DNA base repair in Pyrococcus furiosus
Nucleic Acids Research, 2015Co-Authors: Miyako Shiraishi, Sonoko Ishino, Takeshi Yamagami, Yuriko Egashira, Shinichi Kiyonari, Yoshizumi IshinoAbstract:DNA is constantly damaged by endogenous and environmental influences. Deaminated adenine (hypoxanthine) tends to pair with cytosine and leads to the A:T→G:C transition mutation during DNA replication. Endonuclease V (EndoV) hydrolyzes the second phosphodiester bond 3′ from Deoxyinosine in the DNA strand, and was considered to be responsible for hypoxanthine excision repair. However, the downstream pathway after EndoV cleavage remained unclear. The activity to cleave the phosphodiester bond 5′ from Deoxyinosine was detected in a Pyrococcus furiosus cell extract. The protein encoded by PF1551, obtained from the mass spectrometry analysis of the purified fraction, exhibited the corresponding cleavage activity. A putative homolog from Thermococcus kodakarensis (TK0887) showed the same activity. Further biochemical analyses revealed that the purified PF1551 and TK0887 proteins recognize uracil, xanthine and the AP site, in addition to hypoxanthine. We named this endonuclease Endonuclease Q (EndoQ), as it may be involved in damaged base repair in the Thermococcals of Archaea.
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biochemical characterization of endonuclease v from the hyperthermophilic archaeon pyrococcus furiosus
Journal of Biochemistry, 2014Co-Authors: Shinichi Kiyonari, Sonoko Ishino, Yuriko Egashira, Yoshizumi IshinoAbstract:Endonuclease V (Endo V) is a DNA repair enzyme that recognizes Deoxyinosine and cleaves the second phosphodiester bond on the 3' side of the deaminated base lesion. A database search revealed the presence of homologous genes for Endo V in most archaeal species, but the absence in some methanogenic species. We cloned a gene encoding the sequence homologous to Escherichia coli Endo V from the genome of the hyperthermophilic euryarchaeon, Pyrococcus furiosus and purified gene product (PfuEndoV) to homogeneity. In vitro characterization showed that PfuEndoV possesses specific endonuclease activity for the Deoxyinosine-containing DNA strand. The activity of the enzyme was maximal at 90°C. Stable complex formation between PfuEndoV and nicked DNA produced by the cleavage reaction was detected by gel mobility shift assays. The molecular mechanisms of the inosine repair pathway including Endo V in the archaeal cells are discussed. Interestingly, PfuEndoV cleaved inosine-containing RNA strands as well as DNA substrates. PfuEndoV may also be involved in RNA metabolism.