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J A Martino

Publications and source records attributed to J A Martino.

13 recordsLinked to original sources
PubMed1999

Influence of nucleosome structure on the three-dimensional folding of idealized minichromosomes.

BACKGROUND: The closed circular, multinucleosome-bound DNA comprising a minichromosome provides one of the best known examples of chromatin organization beyond the wrapping of the double helix around the core of histone proteins. This higher level of chain folding is governed by the topology of the constituent nucleosomes and the spatial disposition of the intervening protein-free DNA linkers. RESULTS: By simplifying the protein-DNA assembly to an alternating sequence of virtual bonds, the organization of a string of nucleosomes on the minichromosome can be treated by analogy to conventional chemical depictions of macromolecular folding in terms of the bond lengths, valence angles, and torsions of the chain. If the nucleosomes are evenly spaced and the linkers are sufficiently short, regular minichromosome structures can be identified from analytical expressions that relate the lengths and angles formed by the virtual bonds spanning the nucleosome-linker repeating units to the pitch and radius of the organized quaternary structures that they produce. CONCLUSIONS: The resulting models with 4-24 bound nucleosomes illustrate how a minichromosome can adopt the low-writhe folding motifs deduced from biochemical studies, and account for published images of the 30 nm chromatin fiber and the simian virus 40 (SV40) nucleohistone core. The marked sensitivity of global folding to the degree of protein-DNA interactions and the assumed nucleosomal shape suggest potential mechanisms for chromosome rearrangements upon histone modification.

Chromosomes↗
PubMed1998

Modeling chain folding in protein-constrained circular DNA.

An efficient method for sampling equilibrium configurations of DNA chains binding one or more DNA-bending proteins is presented. The technique is applied to obtain the tertiary structures of minimal bending energy for a selection of dinucleosomal minichromosomes that differ in degree of protein-DNA interaction, protein spacing along the DNA chain contour, and ring size. The protein-bound portions of the DNA chains are represented by tight, left-handed supercoils of fixed geometry. The protein-free regions are modeled individually as elastic rods. For each random spatial arrangement of the two nucleosomes assumed during a stochastic search for the global minimum, the paths of the flexible connecting DNA segments are determined through a numerical solution of the equations of equilibrium for torsionally relaxed elastic rods. The minimal energy forms reveal how protein binding and spacing and plasmid size differentially affect folding and offer new insights into experimental minichromosome systems.

Binding Sites↗
PubMed1997

Modeling protein-induced configurational changes in DNA minicircles.

A method is offered for obtaining minimum energy configurations of DNA minicircles constrained by one or more DNA-binding proteins. The minicircles are modeled as elastic rods, while the presence of bound protein is implied by rigidly fixing portions of these chains. The configurations of the geometrically constrained circular rods are sampled stochastically and optimized according to a simple elastic energy model of nicked DNA. The shapes of the minimum energy structures identified after a simulated annealing process are analyzed in terms of relative protein orientation and writhing number. The procedure is applied to minicircles 500 base pairs in length, bound to two evenly spaced DNA-wrapping proteins. The presence of histone octamers is suggested by rigidly fixing the two protein-bound portions of each minicircle as small superhelices similar in dimension to nucleosomal DNA. The folded minimum energy forms of sample chains with different degrees of protein wrapping are noteworthy in themselves in that they offer a new resolution to the well-known minichromosome linking number paradox and point to future minicircle simulations of possible import.

DNA, Circular↗
PubMed1967

The effects of infusion of water on renal hemodynamics and the tubular reabsorption of sodium.

Anesthetized dogs receiving an infusion of chlorothiazide and ethacrynic acid were given 600-ml infusions of distilled water or dilute dextrose solutions. The absolute rate of tubular sodium reabsorption was depressed, and the glomerular filtration rate was increased during the water loading, despite the associated decreases in plasma sodium concentration and decreases in the filtered load of sodium. The extent to which fractional sodium reabsorption decreased and the excretion of sodium increased was inversely related to the degree to which the filtered load of sodium was depressed as a result of the decreased plasma sodium concentration. We conclude that, in the presence of the diuretic blockade of distal tubular sodium reabsorption, infusion of water depresses proximal tubular reabsorption of sodium and that these changes are qualitatively similar to those previously observed during infusions of saline. Similar depression of tubular reabsorption of sodium and increased excretion of sodium occurred during water loading in the absence of diuretics in dogs undergoing saline diuresis, which presumably provided a high rate of distal sodium reabsorption before water loading. We suggest that volume expansion with water depresses proximal tubular reabsorption of sodium in a manner qualitatively similar to infusions of saline and that the extent to which sodium excretion is increased during water loading is dependent upon 1) the absolute extent to which proximal reabsorption is depressed, 2) the extent to which the filtered load of sodium is maintained in the presence of a falling concentration of sodium in plasma, and 3) the extent to which increased distal reabsorption compensates for the depressed proximal reabsorption of sodium. Mechanisms are suggested whereby the previously reported inverse relationship between plasma concentration of sodium and over-all tubular reabsorption of sodium may be only apparent, and could be the result of physiologic "glomerulotubular balance" during the specific experimental maneuvers.

Animals↗
PubMed1967

Demonstraton of a role of physical factors as determinants of the natriuretic response to volume expansion.

The importance of plasma protein concentration, renal vascular resistance, and arterial pressure as mediators of the natriuretic response to volume expansion was investigated in anesthetized dogs. Saline loading depressed plasma protein concentration and increased arterial pressure but did not decrease renal vascular resistance. Restoring plasma protein concentration by infusing hyperoncotic albumin increased sodium reabsorption and decreased sodium excretion during saline loading despite simultaneous decreases in renal vascular resistance and increases in arterial pressure. Infusion of "plasma" did not depress plasma protein concentration and produced natriuresis associated with increased arterial pressure and marked decreases in renal vascular resistance. Unilateral hemodynamic natriuresis was produced before "plasma" loading by the renal arterial infusion of acetylcholine, and the subsequent infusion of "plasma" resulted in much smaller increases in sodium excretion by the vasodilated kidney than by the control kidney. If perfusion pressure to both kidneys was then reduced by aortic constriction sodium excretion by the vasodilated kidney could be reduced to preloading (vasodilated) levels without reduced glomerular filtration, despite continued natriuresis in control kidneys which underwent vasodilatation in response to the infusion of plasma. Infusion of equilibrated whole blood did not alter plasma protein concentration or the hematocrit, and renal vascular resistance did not decrease. Sodium excretion was increased minimally or not at all by the infusion of blood despite increased arterial pressure and glomerular filtration. However, in kidneys vasodilated before infusing blood sodium excretion increased in response to the infusion in association with increased arterial pressure. This increased excretion of sodium by vasodilated kidneys during infusion of blood could be abolished by reducing perfusion pressure to the preloading level. These observations indicate that changes in plasma oncotic pressure, renal vascular resistance, and arterial pressure either alone or in combination are important variables determining the natriuretic response to volume expansion, and that the relative importance of each of these factors depends on the manner in which volume is expanded (viz., the infusion of saline, plasma, or blood).

Albumins↗
PubMedDate not supplied

Flexing and folding double helical DNA.

DNA base sequence, once thought to be interesting only as a carrier of the genetic blueprint, is now recognized as playing a structural role in modulating the biological activity of genes. Primary sequences of nucleic acid bases describe real three-dimensional structures with properties reflecting those structures. Moreover, the structures are base sequence dependent with individual residues adopting characteristic spatial forms. As a consequence, the double helix can fold into tertiary arrangements, although the deformation is much more gradual and spread over a larger molecular scale than in proteins. As part of an effort to understand how local structural irregularities are translated at the macromolecular level in DNA and recognized by proteins, a series of calculations probing the structure and properties of the double helix have been performed. By combining several computational techniques, complementary information as well as a series of built-in checks and balances for assessing the significance of the findings are obtained. The known sequence dependent bending, twisting, and translation of simple dimeric fragments have been incorporated into computer models of long open DNAs of varying length and chemical composition as well as in closed double helical circles and loops. The extent to which the double helix can be forced to bend and twist is monitored with newly parameterized base sequence dependent elastic energy potentials based on the observed configurations of adjacent base pairs in the B-DNA crystallographic literature.

Base Composition↗