Giovanna Costanzo

One-Pot TiO2-Catalyzed Synthesis of Nucleic Bases and Acyclonucleosides from Formamide: Implications for the Origin of Life

A novel one‐pot TiO2‐catalyzed synthesis of nucleobases and acyclonucleosides from formamide is reported. Since formamide can be formed under prebiotic conditions, these reactions have implications for the origin of life. While a number of purine derivatives have been found as products of non‐TiO2‐catalyzed reactions, important compounds that would not otherwise occur (namely, thymine, 5hydroxymethyluracil, and acyclonucleosides) are formed in acceptable yields by TiO2‐catalyzed reactions. Moreover, TiO2 selectively affects the rates of degradation of nucleobases, as single units and when embedded in polynucleotides.

Advances in the Prebiotic Synthesis of Nucleic Acids Bases: Implications for the Origin of Life

Prebiotic chemistry plays a central role in the investigation of the possible scenarios of the early chemical environments. Its goal is to shed light on the events involved in the synthesis of initial biomolecules and on the self-organization processes that led the last common ancestor. Even though a well defined scenario for the physico-chemical conditions on the primitive Earth is not available, one can assume that a synthetic pathway, in order to be considered prebiotic, should use the simplest chemicals and the most common conditions present at that time. Low molecular weight molecules such as hydrogen cyanide and formaldehyde, easily formed from the primitive atmosphere by ultraviolet light, heat or electric discharge as energy sources, have been considered as prebiotic precursors. Here we focus on the attempts to identify the prebiotic events originating purine and pirimidine nucleic acids bases, the necessary components for the assembling of nucleosides, nucleotides and oligonucleotides. © 2004 Bentham Science Publishers Ltd.

Synthesis and Degradation of Nucleobases and Nucleic Acids by Formamide in the Presence of Montmorillonites

We describe the role of formamide, a product of the hydrolysis of hydrogen cyanide, as precursor of several components of nucleic acids under prebiotic conditions. When formamide is heated in the presence of montmorillonites, the efficient one‐pot synthesis of purine, adenine, cytosine, and uracil is obtained. Along with these nucleobases, several components of the inosine pathway are obtained: 5‐aminoimidazole‐4‐carboxamide, 5‐formamidoimidazole‐4‐carboxamide and hypoxanthine. This almost complete catalogue of nucleic acid precursors is accompanied by N9‐formylpurine, which, containing a masked glycosidic bond in its formyl moiety, is a plausible precursor of purine acyclonucleosides. In addition, montmorillonites differentially affect the rate of degradation of nucleobases when embedded in 2′‐deoxyoligonucleotides; namely, montmorillonites protect adenine and guanine from the degradative action of formamide, while thymine degradation is enhanced. The oligonucleotide backbone reactivity to formamide is also affected; this shows that the interaction with montmorillonites modifies the rate of abstraction of the Hα and Hβ protons on the sugar moieties.

Synthesis and degradation of nucleic acid components by formamide and iron sulfur minerals

We describe the one-pot synthesis of a large panel of nucleic bases and related compounds from formamide in the presence of iron sulfur and iron-copper sulfur minerals as catalysts. The major products observed are purine, 1H-pyrimidinone, isocytosine, adenine, 2-aminopurine, carbodiimide, urea, and oxalic acid. Isocytosine and 2-aminopurine may recognize natural nucleobases by Watson-Crick and reverse Watson-Crick interactions, thus suggesting novel scenarios for the origin of primordial nucleic acids. Since the major problem in the origin of informational polymers is the instability of their precursors, we also investigate the effects of iron sulfur and iron-copper sulfur minerals on the stability of ribooligonucleotides in formamide and in water. All of the iron sulfur and iron-copper sulfur minerals stimulated degradation of RNA. The relevance of these findings with respect to the origin of informational polymers is discussed.

From formamide to RNA: the roles of formamide and water in the evolution of chemical information

In pursuing the origin of informational polymers, we followed the assumption that their spontaneous formation could only have occurred: (i) if all the components were present at the same site and in the same reaction, and (ii) if the thermodynamics of the processes involved favored a polymerized over a monomeric state of the precursors. A plausible scenario satisfying both assumptions is provided.

Attraction, phasing and neighbour effects of histone octamers on curved DNA

Nucleosome core particles were reconstituted on various DNA fragments containing a Crithidia fasciculata kinetoplast curved tract. The results show that, on curved DNA, nucleosome core particles form six- to sevenfold preferentially, relative to bulk sequences. The preferential deposition occurs at multiple periodic positions, whose distribution reveals a unique rotational setting of DNA with respect to the histone octamer surface and whose average periodicity is 10.26 +/- 0.04. Evidence is provided for a context effect in histone octamer deposition: octamers bound to a segment of curved DNA influence the positions of neighbour octamers. Taken together, the preferential formation of nucleosome core particles and the influence on the localization of neighbouring particles suggest for intrinsically bent sequences the biologically relevant role of organizers of nucleosomal arrays.

Formamide as the main building block in the origin of nucleic acids

The simplest molecules grouping the four most common elements of the universe H,C,O and N (with the exception of the biologically inert He) are isocyanate HNCO and formamide H2NCOH. Reasons for the availability of formamide on prebiotic Earth are presented. We review evidence showing that formamide in the presence of largely available catalysts and by moderate heating yields the complete set of nucleic bases necessary for the formation of nucleic acids. Formamide also favours the formation of acyclonucleosides and the phosphorylation and trans-phosphorylation of nucleosides, thus providing a plausible chemical frame for the passage from a simple one-carbon compound to nucleic polymers. Physico-chemical conditions exist in which formamide favours the stability of the phosphoester bonds in nucleic polymers relative to that of the same bonds in monomers. Starting from a formamide-laden environment subject only to the laws of chemistry, a hypothesis is outlined sketching the passage towards an aqueous world in which Darwinian rules apply.

ABFI contributes to the chromatin organization of Saccharomyces cerevisiae ARS1 B-domain

The involvement of the ABFI transcription factor in organizing the chromatin structure of the Saccharomyces cerevisiae ARS1 region has been previously postulated. We studied the ARS1 chromatin structure both on the chromosome and on plasmids carrying wild type or mutated ABFI binding sites, using a recently developed no-background technique for nucleosome mapping, coupled with high resolution micrococcal nuclease in vivo footprinting. We show that ABFI protein acts as a boundary element of chromatin structure, by limiting the invasion by nucleosomes toward the essential A-domain.

Synthesis and degradation of nucleic acid components by formamide and cosmic dust analogues

We show the unprecedented one‐pot synthesis of a large suite of pyrimidines (including cytosine and uracil) and purines from formamide in the presence of cosmic‐dust analogues (CDAs) of olivines. Since the major problem in the origin of informational macromolecules is the instability of their precursors, we also investigate the stabilizing effect of CDAs on the intrinsic instability of oligonucleotides in formamide.

Nonenzymatic RNA Ligation in Water

We describe the nonenzymatic ligation of RNA oligomers in water. Dimers and tetramers are formed in a time-, pH-, and temperature-dependent reaction. Ligation efficiency depends on oligonucleotide length and sequence and is strongly enhanced by adenine-based nucleotide cofactors. Ligation of short RNA fragments could have liberated the prebiotic polymerization systems from the thermodynamically demanding task of reaching a (pre)genetically meaningful size by stepwise addition of one precursor monomer at the time.