1,10-Phenanthroline-cuprous ion complex, a potent inhibitor of DNA and RNA polymerases

D'Aurora, Vito; Stern, Andrew M.; Sigman, David S.

doi:10.1016/0006-291x(78)91348-7

Cited by 46 publications

(17 citation statements)

References 12 publications

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“…11.3. changes in mRNA labeling kinetics (3,36,46,54,72,109) or by quantitating the disappearance of mRNA after the inhibition of transcription (50,90,104) or RNA processing (19,35,47). Those (104), lomofungin (11), or 1,10-phenanthroline (90) is accompanied by inhibition of many other biosynthetic pathways (16,21). Inhibition of RNA processing in tsl36 inhibits the accumulation of all classes of RNA, not just mRNA (35).…”

Section: Discussionmentioning

confidence: 99%

Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae.

1990

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We developed a procedure to measure mRNA decay rates in the yeast Saccharomyces cerevisiae and applied it to the determination of half-lives for 20 mRNAs encoded by well-characterized genes. The procedure utilizes Northern (RNA) or dot blotting to quantitate the levels of individual mRNAs after thermal inactivation of RNA polymerase II in an rpbl-1 temperature-sensitive mutant. We compared the results of this procedure with results obtained by two other procedures (approach to steady-state labeling and inhibition of transcription with Thiolutin) and also evaluated whether heat shock alters mRNA decay rates. We found that there are no significant differences in the mRNA decay rates measured in heat-shocked and non-heat-shocked cells and that, for most mRNAs, different procedures yield comparable relative decay rates. Of the 20 mRNAs studied, 11, including those encoded by HIS3, STE2, STE3, and MATal, were unstable (t112 < 7 min) and 4, including those encoded by ACT) and PGKI, were stable (t112 > 25 min). We have begun to assess the basis and significance of such differences in the decay rates of these two classes of mRNA. Our results indicate that (i) stable and unstable mRNAs do not differ significantly in their poly(A) metabolism; (ii) deadenylation does not destabilize stable mRNAs; (iii) there is no correlation between mRNA decay rate and mRNA size; (iv) the degradation of both stable and unstable mRNAs depends on concomitant translational elongation; and (v) the percentage of rare codons present in most unstable mRNAs is significantly higher than in stable mRNAs.Differences in the decay rates of individual mRNAs can have profound effects on the overall levels of expression of specific genes (80,93). Although the potential importance of mRNA stability as a mechanism for regulating gene expression has been recognized (7, 86), the structures and mechanisms involved in the determination of individual mRNA decay rates have yet to be elucidated. As an approach to understanding the determinants of mRNA stability, we have begun to compare the properties of mRNAs in Dictyostelium discoideum which differ significantly in their respective decay rates (94). In this report, we describe our initial efforts to perform a similar analysis of mRNAs in the yeast Saccharomyces cerevisiae. Our objective was the identification of both stable and unstable yeast mRNAs that were encoded by genes which had already been well characterized. Success in such an endeavor would make it possible to explore the structural determinants of mRNA stability, for example, by analyzing the decay rates of mRNAs transcribed from chimeric genes (25,42,43,81,96,97).Decay rates for both the poly(A)+ RNA population and for individual yeast mRNAs have been measured previously by several different functional or chemical assays. Half-lives ranging from 16 to 23 min have been measured for the average turnover rate of the poly(A)+ RNA population, whereas half-lives of individual mRNAs span a broader range from 1 to over 100 min (3,18,19,35,36,46,47,50,52,54,...

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Section: Discussionmentioning

confidence: 99%

Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae.

1990

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“…The fact that copper(I) complexes of 1,10-phenanthroline have been shown to be potent inhibitors of DNA and RNA polymerases (4) suggests a mode of action in which inhibition of DNA biosynthesis is involved. However, from the ID50 and MIC shown in Table 1, it appears that the copper(I) complex of DMP exerts the strongest activity, whereas D'Aurora et al (4) found this complex to be completely ineffective in inhibiting DNA and RNA polymerases. This discrepancy, combined with the results for macromolecular synthesis (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The copper-chelating agents bathocuproine and bathophenanthroline (which contain a 2,2'-bipyridyl structure) inhibit the ribonucleic acid (RNA)-dependent RNA polymerase activity of some influenza viruses in vitro (20). With 1,10-phenanthroline, inhibition of the RNA-dependent deoxyribonucleic acid (DNA) polymerase of Rous sarcoma virus was found (24), and the copper(I) complex of 1,10-phenanthroline has been reported as a potent inhibitor of various bacterial and bacteriophage DNA and RNA polymerases (4).…”

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confidence: 99%

Mode of action of copper complexes of some 2,2'-bipyridyl analogs on Paracoccus denitrificans

Smit¹,

Goot²,

Nauta³

et al. 1980

Antimicrob Agents Chemother

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Copper complexes of 2,2'-bipyridyl and related compounds and CuSO4 inhibited the growth of paracoccus denitrificans. The copper(I) complex of 2,9-dimethyl-1,10-phenanthroline [Cu(DMP)2NO3] showed the highest activity, whereas the copper(II) complex of 1,10-phenanthroline and CuSO4 inhibited the growth to a lesser extent. The uncomplexed ligands (1,10-phenanthroline and 2,9-dimethyl-1,10-phenanthroline) showed little activity, but in the presence of noninhibitory amounts of CuSO4 this activity increased markedly. Copper ions therefore proved to be essential for the growth-inhibitor effect. The extent of inhibition appeared to be strongly dependent on the initial cell density and on the growth medium. No selective inhibition of deoxyribonucleic acid, ribonucleic acid, or protein synthesis was observed with Cu(DMP)2NO3. Respiratory electron transport of P. denitrificans appeared to be strongly inhibited by Cu(DMP)2NO3 and to a somewhat lesser extent by CuSO4. Both aerobic and anaerobic respirations were inhibited to the same extent, and from the cytochrome redox kinetics it is concluded that the site of this inhibition in the respiratory electron transport chain must be located before cytochrome b. Cu(DMP)2NO3 did not significantly influence the H+/O ratio with whole cells of P. denitrificans, suggesting that the efficiency of oxidative phosphorylation is not affected by CU(DMP)2NO3. Growing cultures of P. denitrificans showed a decrease in intracellular potassium ion content in the presence of increasing amounts of Cu(DMP)2NO3. It is concluded that interference with the cytoplasmic membrane, resulting in inhibition of respiratory electron transport, probably constitutes the main mode of action of copper complexes of 2,2'-bipyridyl analogs on P. denitrificans.

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“…The formation of a noncovalent complex analogous to a Michaelis complex in the cleavage of poly(dA-dT) has already been inferred based on (i) the reactivity of the cuprous complex of 1,10-phenanthroline relative to the reactivities of the cuprous complexes of bipyridine and 2,2',2"-terpyridine (31,32), (ii) the inhibition of the cleavage by intercalating agents (14), and (iii) the lack of reactivity of noncomplement-agents (14), and (iii) the lack of reactivity of noncomplementing single-stranded DNAs such as poly(dT) (14). Although it is tempting to assume that the complex between a B-DNA and (OP)2Cu+ involves intercalation because of the structural similarity of the ligand to ethidium bromide, no firm evidence for this binding mode, as opposed to interaction with the major or minor groove, is available.…”

Section: Discussionmentioning

confidence: 99%

Secondary structure specificity of the nuclease activity of the 1,10-phenanthroline-copper complex.

Pope¹,

Sigman²

1984

Proc. Natl. Acad. Sci. U.S.A.

110

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1,10-Phenanthroline-cuprous ion complex, a potent inhibitor of DNA and RNA polymerases

Cited by 46 publications

References 12 publications

Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae.

Identification and comparison of stable and unstable mRNAs in Saccharomyces cerevisiae.

Mode of action of copper complexes of some 2,2'-bipyridyl analogs on Paracoccus denitrificans

Secondary structure specificity of the nuclease activity of the 1,10-phenanthroline-copper complex.

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