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Inhibition of Eukaryotic DNA Topoisomerase I: Understanding the Mechanisms of Cell Death and Drug Resistance

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Title Inhibition of Eukaryotic DNA Topoisomerase I: Understanding the Mechanisms of Cell Death and Drug Resistance
 
Creator Roy, Amit
 
Subject Infectious Diseases and Immunology
 
Description The helical structure of duplex DNA allows for the faithful duplication and transmission of genetic information
from one generation to the next, at the same time maintaining the integrity of the polynucleotide chains.
The complementary nature of the antiparallel DNA strands enables each to serve as a template for the
synthesis of the respective daughter DNA strands. The intertwining of these polynucleotide chains in
duplex DNA further ensures the integrity of the DNA helix by physically linking the individual strands in a
structure stabilized by hydrogen bonding and stacking interactions between the hydrophobic bases (Bjornsti
and Osheroff, 1999). Soon after the double-helical structure was proposed for DNA (Watson and Crick,
1953a), the replication of the circular DNA molecule of a prokaryote raised an intriguing question: How
did the two sisters double-stranded DNA (dsDNA) molecules disentangle? This mechanical problem of
separating two intertwined chains became a topological one. In such a molecule, the two single stranded
rings are topologically linked and therefore, cannot come apart without at least one transient break in one
of the two strands. The order or extent of topological linkage of the two strands is expressed by their
linking number (Lk). Lk is defined as the number of times the two single strands revolve around each
other. A right handed double helix with n base pairs will make one full turn every 10.5 base pairs under the
physiological conditions in its most stable structure.
 
Date 2009
 
Type Thesis
NonPeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1247/1/Thesis_Amit_Roy.pdf
Roy, Amit (2009) Inhibition of Eukaryotic DNA Topoisomerase I: Understanding the Mechanisms of Cell Death and Drug Resistance. PhD thesis, Jadavpur University.
 
Relation http://www.eprints.iicb.res.in/1247/