Guanosine monophosphate reductase from Artemia salina: inhibition by xanthosine monophosphate and activation by diguanosine tetraphosphate

Renart, Marga F.; Renart, Jaime; Sillero, Marı́a A. Günther; Sillero, Antonio

doi:10.1021/bi00668a003

Cited by 42 publications

(6 citation statements)

References 16 publications

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“…Interestingly, Gp 4 G but not Ap 4 A competitively inhibited both activities of APE1. The intracellular concentration of Gp 4 G in mammalian cells is not clear yet; however, the physiological concentrations of Gp 4 G was shown to be in the nanomolar to micromolar range in rat tissues and human blood platelets (40,41). In addition, the concentrations of Gp 4 G were in the nanomolar to micromolar ranges in Saccharomyces cerevisiae and E. coli cells, depending on the growth condition (37).…”

Section: Nucleosides/nucleotidesmentioning

confidence: 99%

“…It was also proposed that Gp 4 G regulates the activity of endoribonuclease VI in Artemia, by alternating its concentration under different developmental stages (39). An in vitro experiment has shown that Gp 4 G activates GMP reductase activity in both Artemia and human erythrocytes at nanomolar concentrations (41,42). Grau et al (43) proposed a relationship between Gp 4 G binding capacity and the time of development of rat embryos.…”

Section: Nucleosides/nucleotidesmentioning

confidence: 99%

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The Exonuclease Activity of Human Apurinic/Apyrimidinic Endonuclease (APE1)

Chou

Cheng

2003

Journal of Biological Chemistry

103

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Human DNA apurinic/apyrimidinic endonuclease (APE1) plays a key role in the DNA base excision repair process. In this study, we further characterized the exonuclease activity of APE1. The magnesium requirement and pH dependence of the exonuclease and endonuclease activities of APE1 are significantly different. APE1 showed a similar K m value for matched, 3 mispaired, or nucleoside analog ␤-L-dioxolane-cytidine terminated nicked DNA as well as for DNA containing a tetrahydrofuran, an abasic site analog. The k cat for exonuclease activity on matched, 3 mispaired, and ␤-L-dioxolane-cytidine nicked DNA are 2.3, 61.2, and 98.8 min ؊1 , respectively, and 787.5 min ؊1 for APE1 endonuclease. Site-directed APE1 mutant proteins (E96A, E96Q, D210E, D210N, and H309N), which target amino acid residues in the endonuclease active site, also showed significant decrease in exonuclease activity. DNA base excision repair is the main pathway to repair DNA base damages caused by oxidation, radiation, and the loss of bases (1, 2). There are several enzymes that participate in this pathway, including DNA polymerase ␤, DNA ligase III-XRCC1 complex (1, 2), and apurinic/apyrimidinic endonuclease (APE1) 1 to protect the genome integrity (1-3). The DNA repair activity of APE1 resides in the C-terminal region (4, 5). It endonucleolytically makes a nick immediately adjacent to 5Ј of an apurinic/apyrimidinic (AP) site and generates a hydroxyl group at the 3Ј terminus upstream of the nick and a 5Ј-deoxyribose phosphate moiety downstream (6). DNA polymerase ␤ further processes the product of APE1 by inserting a nucleotide into the gap and releasing the 5Ј-deoxyribose phosphate by its intrinsic lyase activity (7). The repair process is then completed by either DNA ligase I or DNA ligase III/XRCC1 to seal the nicked DNA (1). During DNA base excision repair, DNA polymerase ␤ is the major polymerase that incorporates a nucleotide into the gapped DNA (1). However, DNA polymerase ␤ is a lower fidelity polymerase (8) in comparison to the replicating DNA polymerases ␦ or ⑀ (9). ⌻he error rate of polymerase ␤ is about 1 in 4000 incorporations (1).APE1 is a versatile multifunctional protein (10). In addition to its endonuclease activity, it also possesses 3Ј-phosphatase, 3Ј-phosphodiesterase, RNase H, and 3Ј-5Ј-exonuclease activities (10). APE1 knockout mice die in the early embryonic stage (11), which indicates this protein is critical for development. Previously we reported (12) that the 3Ј-5Ј-exonuclease activity of APE1 is the major exonuclease activity in the human cell nucleus for the removal of the nucleoside analog ␤-L-dioxolanecytidine (L-OddC, BCH-4556, Troxacitabine, and Troxatyl) from the 3Ј termini of DNA. L-OddC is a novel nucleoside analog with L-configuration that is currently under phase III clinical trial and is showing promising activity for the treatment of leukemia (13,14). The incorporation of L-OddC into DNA terminates DNA chain elongation because of the lack of the 3Ј-hydroxyl group on the sugar moiety of L-OddC. The cytotoxicity ...

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Section: Nucleosides/nucleotidesmentioning

confidence: 99%

Section: Nucleosides/nucleotidesmentioning

confidence: 99%

The Exonuclease Activity of Human Apurinic/Apyrimidinic Endonuclease (APE1)

Chou

Cheng

2003

Journal of Biological Chemistry

103

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“…Recent evidence points to a regulatory role for these compounds. Gp4G is an activator, at nanomolar concentration, of GMP reductase from A rtemia and erythrocytes (Renart et al, 1976;Spector et al, 1979). The amount of Ap4A present in mammalian cells varies in parallel with the proliferative activity of the culture (Rapaport & Zamecnik, 1976), and it has been proved that the synthesis of DNA is elicited by Ap4A in cells arrested in G, phase (Grummt, 1978).…”

mentioning

confidence: 99%

Bis-(5'-guanosyl) tetraphosphatase in rat tissues.

Cameselle¹,

Costas²,

Sillero³

et al. 1982

Biochemical Journal

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The occurrence and distribution of bis-(5'-guanosyl) tetraphosphatase activity towards dinucleoside tetraphosphates between the 27 000 g supernatant and sedimented fraction were studied in liver, kidney, brain, muscle and intestinal mucosa from rat. The p1p4-bis-(5'-guanosyl) tetraphosphate-hydrolysing activities found in total homogenates were 0.77, 1.44, 0.39, 0.36 and 2.14 units (mumol/min)/g respectively. The activities found in the 27000 g-sedimented fractions were 74, 49, 11, 4 and 96% of those present in the homogenates respectively. The properties of the soluble enzymes were investigated. All of them have low Km values for p1p4-bis-(5'-guanosyl) tetraphosphate (from 2 to 50 microM), are competitively inhibited by guanosine 5'-tetraphosphate with K1 values from 10 to 160 nM, have molecular weights of about 21 000, require Mg2+ or Mn2+ and are inhibited by Ca2+. These properties show that bis-(5'-guanosyl) tetraphosphatase (EC 3.6.1.17), an enzyme previously characterized in Artemia salina and rat liver [Warner & Finamore (1965) Biochemistry 4, 1568-1575; Vallejo, Sillero & Sillero (1974) Biochim, Biophys. Acta 358, 117-125; Lobatón, Vallejo, Sillero & Sillero (1975) Eur. J. Biochem. 50, 495-501], is present in all the rat tissues examined. The inhibition of the enzyme by Ca2+ could be related to the effect of p1p4-bis-(5'-adenosyl) tetraphosphate as a trigger of DNA synthesis [Grummt, Waltl, Jantzen, Hamprecht, Huebscher & Kuenzle (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 6081-6085].

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“…In embryos of the brine shrimp, A/-tenzicl scilinti, Gp4G appears to be the primary source of cellular purines and phosphate-bond energy for development (3,15) but this nucleotide may also play an important role during development as a regulator of GMP reductase (16) and DNA synthesis (17).…”

Section: Discussionmentioning

confidence: 99%

The diguanosine nucleotides: do they exist in aquatic fungi?

Warner¹,

Thomas²,

Shridhar³

et al. 1977

Can. J. Biochem.

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The aquatic fungi Achlya ambisexualis and Blastocladiella emersonii were grown in the presence of 32Pi and the 32P-labeled acid-soluble nucleotide fractions were analyzed by ion-exchange chromatography on DEAE-cellulose. Selected column fractions containing diguanosine tri- and tetra-phosphates (Gp3G and Gp4G) added as chromatographic markers were analyzed further for 32P by chromatography and (or) enzyme hydrolysis. The results of these experiments clearly indicate that neither Gp4G nor Gp3G is synthesized during vegetative growth of these organisms and cast doubt on the hypothesis that diguanosine nucleotides are important metabolic regulators in fungi.

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Guanosine monophosphate reductase from Artemia salina: inhibition by xanthosine monophosphate and activation by diguanosine tetraphosphate

Cited by 42 publications

References 16 publications

The Exonuclease Activity of Human Apurinic/Apyrimidinic Endonuclease (APE1)

The Exonuclease Activity of Human Apurinic/Apyrimidinic Endonuclease (APE1)

Bis-(5'-guanosyl) tetraphosphatase in rat tissues.

The diguanosine nucleotides: do they exist in aquatic fungi?

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