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J Ninio

Publications and source records attributed to J Ninio.

At least 37 records · Page 2Linked to original sources
PubMed1987

Variations with position of replication errors due to exonuclease warm-up.

A.A mismatch errors occurring during poly(dA) replication with the Klenow fragment of E. coli DNA polymerase I have been quantified. The A/T ratio measured for chains extended by 1-25 nucleotides decreases by a factor of at least 15 from beginning to end. The deduced true error rate may decrease by a factor of 2.5 at each successive nucleotide addition. When ddATP is used instead of dATP, the ddA/T ratio indicates little variation of the misincorporation probability with position. Thus, the accuracy improvement in the first case is due to a warm-up of the proofreading function.

Base Composition↗
PubMed1987

Catalysis by a prebiotic nucleotide analog of histidine.

A ribosylated derivative of adenine, N6 ribosyl adenine, likely to have formed under prebiotic synthesis conditions, is shown to be as active as histidine in the model reaction of p-nitrophenyl acetate hydrolysis. This property widens the range of reactions accessible to RNA catalysis.

Adenosine↗
PubMed1987

Alternative to the steady-state method: derivation of reaction rates from first-passage times and pathway probabilities.

An alternative method for deriving rate equations in enzyme kinetics is presented. An enzyme is followed as it moves along the various pathways allowed by the reaction scheme. The times spent in various sections of the scheme and the pathway probabilities are computed, using simple rules. The rate equation obtains as a function of times and probabilities. The results are equivalent to those provided by the steady-state formalism. While the latter applies uniformly to all schemes, the formalism presented here requires adaptation to each additional class of schemes. However, it has the merit of allowing one to leave unspecified many details of the scheme, including topological ones. Furthermore, it allows one to decompose a scheme into subschemes, analyze the parts separately, and use the intermediate results to derive the rate equation of the complete scheme. The method is applied here to derive general equations for one- and two-entry site enzymes.

Binding Sites↗
PubMed1986

Mnemonic aspects of Escherichia coli DNA polymerase I. Interaction with one template influences the next interaction with another template.

When Escherichia coli DNA polymerase I (Pol I) replicates a homopolymer, the excision/polymerization (exo/pol) ratio varies with enzyme and initiator concentration. The study of this effect in the case of poly(dA).oligo(dT) replication led us to propose a mnemonic model for Pol I, in which the 3' to 5' excision activity warms up when the enzyme is actively polymerizing, and cools down when it dissociates from the template. The model predicts that the exo/pol ratio must increase with processivity length and initiator concentration and decrease with enzyme concentration. It predicts also that contact of the enzyme with one template alters its excision efficiency towards another template. The exo/pol ratio and processivities of Pol I and its Klenow fragment were studied on four templates: poly(dA).(dT)10, poly(dT).(dA)10, poly(dC).(dG)10 and poly(dI).(dC)10. We show that the Klenow fragment is usually much less processive than Pol I and when this is the case it has a much lower exo/pol ratio. At equal processivity, the exo/pol ratios are nearly equal. Furthermore, many factors that influence processivity length (e.g. manganese versus magnesium, inorganic pyrophosphate, ionic strength) influence the exo/pol ratio in the same direction. The study of deaminated poly(dC) replication, where we followed incorporation and excision of both G and A residues, allowed us to assign the origin of the dNMP variations to changes in the 3' to 5' proof-reading activity of Pol I. Similarly, the lower dNMP turnover of the Klenow fragment observed with deaminated poly(dC) was specifically assigned to a decreased 3' to 5' exonuclease activity. The exo/pol ratio generally increased with initiator and decreased with enzyme concentration, in agreement with the model, except for poly(dI).oligo(dC), where it decreased with initiator concentration. However, by terminating chain elongation with dideoxy CTP, we showed directly that, even in this system, excision is relatively inefficient at the beginning of synthesis. Interaction of Pol I with poly(dA).(dT) or with poly(dC).(dG) modifies its exo/pol characteristics in the replication of poly(dI).(dC) and poly(dA).(dT), respectively. The Klenow enzyme is not sensitive to such influences and this correlates with its reduced processivity on the influencing templates. Our results reveal the existence of differences between Pol I and its Klenow fragment that are more profound than has been thought previously.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Composition↗
PubMed1986

Fine tuning of ribosomal accuracy.

If the rate constant for peptide bond formation were high just after an amino acid incorporation and occasionally switched to a lower value afterwards, then the ribosome could compensate for tRNA imbalance specifically at hungry codons. A rigorous analysis of the scheme proves its effectiveness. For instance, a 10-fold reduction in cognate tRNA concentration may increase the error rate by only a factor of two.

Codon↗
PubMed1985

Graphical coding of nucleic acid sequences.

When, in a nucleic acid sequence, the four letters C, G, A, T (or U) are replaced by suitable graphical symbols, some patterns become immediately apparent. Two sets of symbols, constructed for the analysis of either purine/pyrimidine alternations, or of regions of complementarity within a sequence are shown. In addition, another mode of coding is presented, in which the four letters are represented by vectors. The sequence is thus transformed into a planar trajectory. We show, in the case of the gene for human beta hemoglobin, that such a coding enables an easy discrimination between introns and exons.

Base Sequence↗
PubMed1985

[Prediction of secondary structures of nucleic acids: algorithmic and physical aspects].

Prediction of secondary structures in nucleic acids requires both an adequate physical model and powerful calculation algorithms. In our approach, we cut the molecules in sections of which the contributions to the global energy are context-dependent but roughly additive. The structure of minimum energy is obtained by a tree search under constraints of binary incompatibilities. Our algorithm of the "incompatibility islets" is shown to be more powerful than the "bit parallel forward checking" algorithm, well known in Artificial Intelligence. Recurrent algorithms, proposed by other authors are even more rapid, but often miss the correct structures, for they demand a strict additivity of the energetic contributions, physically unjustified. New strategies, required to deal with molecules of more than 200 nucleotides are discussed. Our physical model has been improved by considering the special case of internal loops beginning with a G-A opposition. A bonus of 1.5 kcal. is attributed to such a feature, at each side of an internal loop. To illustrate our programs, we give the computed schemes for the 3' termini of the small subunit ribosomal RNA.

Base Sequence↗
PubMed1985

Orientational versus horizontal disparity in the stereoscopic appreciation of slant.

Twenty stereograms with needles either plunging in depth or untilted were constructed. When the geometry of the needles was unbiased, the tilt of the needles was correctly and rapidly appreciated. When the needles were biased so as to remove either their orientational disparity, or the difference in horizontal disparities at the tips, they could be seen, depending on the subject and the nature of the bias, either with or without slant. Orientational disparity proved to be, with two different testing methods, clearly more effective than horizontal disparity in conveying the information of slant. Biased needles at -45 degrees were more often rejected as untilted than biased needles at +45 degrees. The orientational disparity information was ineffective with crosses that combined +45 degrees and -45 degrees needles. The reaction time and the nature of the percept were correlated, the tilted percept taking longer to mature than the untilted one in biased stereograms. Of the seventy tested subjects, one appeared to make no use at all of horizontal disparity in the stereoscopic appreciation of slant.

Cues↗
PubMed1985

Errors in the stereoscopic separation of surfaces represented with regular textures.

Stereograms containing two similar or dissimilar linear textures, either on the same surface or at two different depths, were tested on seventy subjects. Whereas random textures usually produced correct percepts, regular textures consistently led to errors of stereoscopic interpretations, including a reversal of hollows into bumps, dissociation of single surfaces into two layers, and errors in relative positioning of two surfaces. Horizontal-vertical textures tended to be seen as flatter and further away from the observer than diagonal ones. Continuous textures tended to be seen closer than discontinuous ones. In the interpretation of the results, the possibility is raised that different textures are processed independently and that the brain has no reliable method for combining the conclusions into a rigorous global percept.

Brain↗
PubMed1984

An energy model that predicts the correct folding of both the tRNA and the 5S RNA molecules.

A new set of energy values to predict the secondary structures in RNA molecules has been derived through a multiple-step refinement procedure. It achieves more than 80% success in predicting the cloverleaf pattern in tRNA (200 sequences tested) and more than 60% success in predicting the consensus folding of 5S RNA (100 sequences). Improvements in our initial program for predicting secondary structures, based on the principle of the "incompatibility islets" made possible the work on 5S RNA. The program was speeded up by introducing a dynamic grouping of the islets into three disjoint blocks. The novel features in the energy model include i) an evaluation of the contribution of odd pairs according to their position within a segment ii) a penalty for internal loops related to their dissymmetry iii) a bonus for bulge loops when the two terminal paired bases at the junction point are both pyrimidines.

Computers↗
PubMed1984

A memory effect in DNA replication.

A study of the polymerization/excision ratio in the replication of poly(dA), primed with oligo(dT), was carried out with E. coli DNA polymerase I, at various primer and enzyme concentrations. The variations in this ratio suggest that 1) the DNA polymerase is able to switch between two states of low and high exonuclease activities and 2) after dissociating from the template, the DNA polymerase drifts towards the low exonuclease state. The recovery of the high exonuclease state would require several successive incorporations.

DNA Polymerase I↗
PubMed1983

The brain as a geometer.

The fragmentary cues we have on the geometric aptitudes of the brain (e.g., in evaluating shapes or appreciating depth) do not lead to a unified model of perceptual geometry. In parallel with physiological studies, aimed at explaining how perception works, I suggest developing the study of the geometrical capabilities of the brain, in order to learn precisely what is accomplished.

Brain↗
PubMed1982

Efficient algorithms for folding and comparing nucleic acid sequences.

Fast algorithms for analysing sequence data are presented. An algorithm for strict homologies finds all common subsequences of length greater than or equal to 6 in two given sequences. With it, nucleic acid pieces five thousand nucleotides long can be compared in five seconds on CDC 6600. Secondary structure algorithms generate the N most stable secondary structures of an RNA molecule, taking into account all loop contributions, and the formation of all possible base-pairs in stems, including odd pairs (G.G., C.U., etc.). They allow a typical 100-nucleotide sequence to be analysed in 10 seconds. The homology and secondary structure programs are respectively illustrated with a comparison of two phage genomes, and a discussion of Drosophila melanogaster 55 RNA folding.

Animals↗
PubMed1980

[Fidelity of a polymerization reaction according to the proximity to equilibrium].

Pyrophosphorolysis, the reverse reaction of nucleotide polymerisation during replication or transcription must influence error-rates. Calculations suggest, for a wide range of reaction mechanisms, a linear dependency between pyrophosphate concentration and the ratio correct/incorrect substrate incorporation. Errors in A.T -rich regions should be particularly sensitive to changes in pyrophosphate concentration.

DNA↗