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A Tyrosyl DNA Phosphodiesterase 1 from Kinetoplastid Parasite Leishmania Donovani (LdTdp1) Capable of Removing topo I–DNA Covalent Complexes

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Title A Tyrosyl DNA Phosphodiesterase 1 from Kinetoplastid
Parasite Leishmania Donovani (LdTdp1) Capable of Removing
topo I–DNA Covalent Complexes
 
Creator Banerjee, Bijoylaxmi
Roy, Amit
Sen, Nilkantha
Majumder, Hemanta K
 
Subject Infectious Diseases and Immunology
 
Description Tyrosyl DNA phosphodiesterase 1 (Tdp1) is a member
of phospholipase D superfamily, which cleaves a
broad range of 3�-DNA adducts, the best characterized
of which is the phosphodiester bond formed
between DNA and topoisomerase IB. This study
describes cloning and functional characterization of
the enzyme, termed as LdTdp1 in the kinetoplastid
parasite Leishmania donovani. Sequence analysis
confirmed conservation of the active site motifs
typical for all Tdp1 proteins. LdTdp1 activity was
detected in the parasite nucleus as well as in the
kinetoplast. The enzyme harbours a nuclear localization
signal at its C-terminus. Overexpression of the
active enzyme protected the parasites against topoisomerase
IB inhibitor camptothecin (CPT) and oxidative
agent H2O2-mediated cytotoxicity and its
downregulation rendered the parasites hypersensitive
to CPT. Trapping of mutant LdTdp1 on DNA takes
place following CPT treatment in L. donovani cells.
The expression level and associated activity of
LdTdp1 were found to be higher in CPT-resistant L.
donovani parasites. Altogether, this is the first report
of Tdp1 from the kinetoplastid parasite L. donovani,
which actively participates in topoisomerase
I-mediated DNA damage repair process and thereby
counteracts the cytotoxic effect of topoisomerase I
inhibitors.
 
Date 2010
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/77/1/MOLECULAR_MICROBIOLOGY_78(1)119%2D137;2010[26].pdf
Banerjee, Bijoylaxmi and Roy, Amit and Sen, Nilkantha and Majumder, Hemanta K (2010) A Tyrosyl DNA Phosphodiesterase 1 from Kinetoplastid Parasite Leishmania Donovani (LdTdp1) Capable of Removing topo I–DNA Covalent Complexes. Molecular Microbiology, 78 (1). pp. 119-137.
 
Relation http:/dx.doi.org/10.1111/j.1365-2958.2010.07318.x
http://www.eprints.iicb.res.in/77/