Biomedical subjects

H Arthanari

Publications and source records attributed to H Arthanari.

4 recordsLinked to original sources

PubMed2001

Functional and dysfunctional roles of quadruplex DNA in cells.

A number of biological roles have been proposed for quadruplex, also referred to as G4 or tetraplex, DNA. The presence of quadruplex DNA may lead to errors in some biological processes and be required in others. Proteins that interact with quadruplex DNA have been identified including those that cause Bloom's and Werner's syndromes. There are small molecules that specifically bind to quadruplex DNA, inhibit telomerase, and are cytotoxic towards tumor cells indicating a role for quadruplex DNA in telomere function. It is now possible to make testable proposals for the possible biological implications of quadruplex DNA in replication, transcription, and recombination as well as possible routes to therapeutic intervention.

Animals↗

PubMed2000

Flexibility and curvature of duplex DNA containing mismatched sites as a function of temperature.

The flexibility and curvature of duplex DNAs containing mismatched sites have been monitored as a function of temperature. The diffusion coefficients are dependent on the flexibility and the curvature of the DNA, and these have been determined by NMR-based methods. The diffusion coefficients, D, depend on a Boltzmann term and the viscosity of the solvent, eta, which is also temperature dependent. To analyze the temperature dependence of the diffusion results, the shape function, S(f) = etaD/T, is used. The shape functions do not have the viscosity and temperature dependence of the diffusion coefficients. The presence of mismatched sites significantly enhances the shape function of duplex DNA at all temperatures examined. The observed increases in the shape functions are attributed to the mismatched sites acting as localized flexible joints. The results on the temperature dependence of the shape functions, the optical absorbance, and the proton chemical shifts indicate that local melting at, and adjacent to, mismatched site occurs at a lower temperature than the overall melting of the duplexes. The localized melting gives rise to a considerable increase in the shape function. The contribution of the curvature of the mismatched sites to the enhanced diffusion has been examined. A DNA with mismatches that are in phase with respect to the helical repeat and a DNA which has the mismatches out of phase with respect to the helical repeat have been examined. The results indicate that mismatched sites have modest curvature.

Base Pair Mismatch↗

PubMed1999

Porphyrins can catalyze the interconversion of DNA quadruplex structural types.

The binding of porphyrins to quadruplex DNAs provides a model system for the examination of drug binding to telomere, centromere, triplet repeat and other DNAs which may form quadruplex structures in vivo. Porphyrins, and certain other molecules that interact with quadruplex DNAs, have been shown to have significant biological activity. In this investigation the interactions of porphyrins with quadruplex DNAs have been examined by optical and NMR methods. The fluorescence of selected porphyrins can be used to discriminate between duplex and quadruplex DNAs. The fluorescence of the porphyrins can also be used to discriminate partially between the chair, basket and parallel stranded types of quadruplex DNA. At the relatively high DNA concentrations used in NMR, the porphyrins catalyze the conversion of both chair and basket type structures into parallel strand quadruplex DNAs. A DNA-porphyrin system has been found which appears to be a model for an intermediate of the catalytic pathway.

Catalysis↗

PubMed1998

Fluorescent dyes specific for quadruplex DNA.

Fluorescent dyes which are specific for duplex DNA have found a wide range of applications from staining gels to visualization of chromosomes. Porphyrin dyes have been found which are highly fluorescent in the presence of quadruplex but not duplex DNA. These dyes may offer a route to the specific detection of quadruplex DNA under biologically important conditions. There are three types of DNA quadruplex structures, and these may play important roles in telomere, centromere, triplet repeat, integration sites and other DNAs, and this first set of porphyrin dyes show some selectivity between the quadruplex types.

Animals↗