Telomere, telomerase, tumorigenesis and therapy: an overview.

The ends of chromosome in higher eukaryote are termed telomere. The DNAs present at that part of chromosome is called telomeric DNA. Telomeric DNA consists of tandemly repeated DNA sequences. The replication of the ends of chromosomes is not controlled by conventional DNA polymerases rather a special kind of enzyme is involved in this process. It is a ribonucleoprotein and known as telomerase. Cells in senescence stage face telomeric crisis that leads to loss of telomeric ends. Surveillance turns to procancer cells with increased telomerase activity which is a later consequence. Based on these facts a key diagnostic approach has been developed for detection of tumour. A novel therapy for tumour repression has been developed using telomerase inhibitors. However, these inhibitors are very much effective for solid tumour therapy and conceptually will not work on hematological malignancies.

Kinetoplast DNA minicircle binding proteins in a Leishmania Spp: interference of protein DNA interaction by berenil.

A kinetoplast DNA minicircle of a Leishmania Spp. binds to several proteins of the kinetoplast Lysates of kinetoplasts of Leishmania grown in the presence of berenil show complete disappearance of some of these protein bands, while the rest of the proteins present appear as much less intense bands in South Western blots when probed with either the conserved or variable regions of the minicircle or whole minicircle DNA. The conserved region of minicircle DNA complexed with berenil in vitro also fails to interact with the DNA binding proteins of kinetoplast of untreated cell in South Western blots. Since berenil induces dyskinetoplasty of kinetoplastidae, the results indicate that interference of protein-DNA interaction in the presence of berenil may be the primary event in making organisms dyskinetoplastic.

A type 1 DNA topoisomerase from the kinetoplast hemoflagellate Leishmania donovani.

A type 1 DNA topoisomerase has been purified from the nuclei of the kinetoplast hemoflagellate Leishmania donovani using polyethylene glycol fractionation and chromatography on hydroxylapatite, phosphocellulose and phenylsepharose column. The relaxation activity is ATP independent. Mg2+ is an essential cofactor for the reaction with an optimum at 10 mM. Mg2+ can be substituted by Mn2+ at 5 mM concentration. The relaxation reaction exhibits a salt optimum at 100 mM KCl. The enzyme can not remove supercoils from positive superhelical DNAs nor can induce supercoiling of relaxed DNAs. The topoisomerase activity is associated with a polypeptide of molecular weight about 67 kDa as shown by sephacryl-S200 gel filtration and by electrophoresis on sodium dodecyl sulphate-polyacrylamide gels.