Ashoke Ranjan Thakur

Sequence Directed Flexibility of DNA and the Role of Cross-strand Hydrogen Bonds

Persistence length and torsional rigidity for different B-DNA sequences have been calculated by analysing crystal structure database. The values of these parameters for mixed sequence DNA are in good agreement with those estimated by others. Persistence lengths for the homopolymeric sequences, namely poly(dA).poly(dT) and poly(dG).poly(dC), are significantly large compared to those of others as expected from the inability of these sequences to form nucleosome under normal conditions. The heteropolymeric sequences poly(dA-dC).poly(dG-dT) and poly(dG-dC).poly(dG-dC), on the other hand, have smaller persistence lengths. This implies larger flexibility of the d(AC).d(GT), d(CA).d(TG), d(GC).d(GC) and d(CG).d(CG) doublets, some of which constitute the genetic disease forming triplet repeats d(CTG).d(CAG) and d(CGG).d(CCG). Thus it is expected that these triplet repeat sequences are also flexible and wrap around the histone octamer efficiently. Persistence length calculations also indicate larger flexibility for these triplet repeat sequences. Furthermore, our computations reveal that the rigidity of a given DNA sequence is controlled by its ability to form cross-strand bifurcated hydrogen bonds between the successive base pairs. Molecular orbital calculations suggest that these hydrogen bonds are generally extended with bond lengths around 3A.

Effect of heavy ion irradiation on DNA DSB repair in Methanosarcina barkeri

Archaea are expected to be highly repair proficient since they survived the vicious onslaught of radiation damage at the time of their early appearance. The DNA double strand break repairing ability of mesophilic archaea Methanosarcina barkeri (DSM 804) was studied using (7)Li, (12)C and (16)O heavy ions and compared with that of (60)Co gamma-rays. They can repair double strand breaks and, as in eukaryotes, the nature as well as extent of induction and its subsequent repair were dependent on the linear energy transfer of the radiation source.

Denaturation of supercoiled DNA: a Monte Carlo study

A theoretical investigation of the denaturation characteristics of a supercoiled DNA has been presented employing a Metropolis Monte Carlo algorithm to examine the overall melting profiles of a supercoiled plasmid as the temperature is varied. We show that in contrast to a previously presented algorithm, this much simpler method is sufficient to explain almost all the overall denaturation characteristics and it also correctly calculates the detailed denaturation probabilities of each base pair at various degrees of supercoiling. We also present for the first time a theoretical investigation of the alkaline denaturation of a supercoiled plasmid. Although one can qualitatively reproduce the denaturation profiles using the present Monte Carlo algorithm, the agreement with experiment is not as good as in the case of thermal denaturation. The possible sources of discrepancy between theory and experiment have been discussed.

Nucleosomal positioning and genetic divergence study based on DNA flexibility map.

Abstract Based on worm like chain model, DNA structural parameters—tilt, roll and rise, derived from crystallographic database have been used to determine the flexibility of DNA that regulates the nucleosomal translational positioning. Theoretically derived data has been compared to the experimental values available in Ioshikhes and Trifonovs database. The methodology has been extended to determine the flexibility of 18S rRNA genome in eukarya, where yeast shows a distinct difference when compared with mammals like human, mouse and rabbit.

Computational approach to the study of supercoil-induced structural polymorphism in DNA

Abstract The superhelical strain in a closed circular B DNA molecule may be relieved at the cost of local conformational transitions to non-B forms wherever possible. Some of these transitions, such as the supercoil-induced B-Z transition in a short purine-pyrimidine stretch, are known to be highly cooperative and can be described in terms of a two-state approximation for the relevant chain partition function. How the presence of DNA-binding ligands may affect such transitions within the supercoiled molecule has been analysed. The result of a preliminary investigation into the effect of sharp bends in the supercoiled DNA structure is also reported.