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Molecular Analysis of Programmed Cell Death by DNA Topoisomerase Inhibitors in Kinetoplastid Parasite Leishmania

  • Nilkantha Sen
  • Bijoylaxmi Banerjee
  • Hemanta K. Majumder
Part of the Molecular Biology Intelligence Unit book series (MBIU)

Abstract

DNA topoisomerases of kinetoplastid parasites represent a family of DNA processing enzymes that essentially solve the topological problems not only in nuclear DNA but also in kinetoplastid DNA. Due to their indispensable function in cell biology they are valuable potential targets for many antileishmanial drugs to induce programmed cell death (PCD). PCD is thought to have evolved to regulate growth and development of multicellular organisms. Kinetoplastid organisms have developed an altruistic mechanism to promote and maintain the clonality within their population. Characterization of PCD by topoisomerase inhibitors could provide information regarding their pathogenesis which could be exploited to develop new targets to limit their growth and treat the disease they cause.

DNA topology affects fundamental processes of life and DNA topoisomerases constitute a growing family of nuclear enzymes that regulate unconstrained DNA supercoils in all living species, bacteria, archea, kinetoplastids and eukaryotes. Changes in DNA topology are required for virtually all DNA dependent events such as DNA replication, transcription, recombination, repair, nucleosome remodeling, chromosome condensation and segregation.1,2 Topoisomerases are divided into two classes, based primarily on their mode of cleaving DNA. Type I DNA topoisomerases act by making a transient nick on a single strand of duplex DNA, passing another strand through the nick and changing the linking number by one unit.3 Type II topoisomerases act by transiently nicking both strands of the DNA, passing another double stranded DNA segment through the gap and changing the linking number by two with the help of ATP molecules.4

Keywords

Trypanosoma Brucei Death Induce Signal Complex Cleavage Complex Leishmania Donovani Kinetoplastid Parasite 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  • Nilkantha Sen
    • 1
  • Bijoylaxmi Banerjee
    • 1
  • Hemanta K. Majumder
    • 1
  1. 1.Division of Molecular ParasitologyIndian Institute of Chemical BiologyKolkataIndia

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