In vivo inhibition of trypanosome mitochondrial topoisomerase II: Effects of kinetoplast DNA maxicircles

Kinetoplast DNA, the mitochondrial DNA of trypanosomes, is a topologically complex structure composed of interlocked minicircles and maxicircles. We previously reported that etoposide, a potent inhibitor of topoisomerase II, promotes the cleavage of about 20% of network minicircle DNA (T. A. Shapiro...

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Main Authors: Shapiro, T.A., Showalter, F.
Format: Journal Article
Language:Inglés
Published: Informa UK Limited 1994
Subjects:
Online Access:https://hdl.handle.net/10568/33069
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author Shapiro, T.A.
Showalter, F.
author_browse Shapiro, T.A.
Showalter, F.
author_facet Shapiro, T.A.
Showalter, F.
author_sort Shapiro, T.A.
collection Repository of Agricultural Research Outputs (CGSpace)
description Kinetoplast DNA, the mitochondrial DNA of trypanosomes, is a topologically complex structure composed of interlocked minicircles and maxicircles. We previously reported that etoposide, a potent inhibitor of topoisomerase II, promotes the cleavage of about 20% of network minicircle DNA (T. A. Shapiro, V. A. Klein, and P. T. Englund, J. Biol. Chem. 264:4173-4178, 1989). We now find that virtually all maxicircles are released from kinetoplast DNA networks after trypanosomes are treated with etoposide. As expected for a topoisomerase II cleavage product, the linearized maxicircles have protein bound to both 5' ends. After etoposide treatment, the residual minicircle catenanes have a sedimentation coefficient which is only 70% that of controls, and by electron microscopy the networks are less compact. Double-size networks, the characteristic dumbbell-shape forms that normally arise in the final stages of network replication, are replaced by aberrant unit-size forms.
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spelling CGSpace330692024-05-01T08:15:18Z In vivo inhibition of trypanosome mitochondrial topoisomerase II: Effects of kinetoplast DNA maxicircles Shapiro, T.A. Showalter, F. trypanosome dna mitochondria animal diseases cell biology molecular biology Kinetoplast DNA, the mitochondrial DNA of trypanosomes, is a topologically complex structure composed of interlocked minicircles and maxicircles. We previously reported that etoposide, a potent inhibitor of topoisomerase II, promotes the cleavage of about 20% of network minicircle DNA (T. A. Shapiro, V. A. Klein, and P. T. Englund, J. Biol. Chem. 264:4173-4178, 1989). We now find that virtually all maxicircles are released from kinetoplast DNA networks after trypanosomes are treated with etoposide. As expected for a topoisomerase II cleavage product, the linearized maxicircles have protein bound to both 5' ends. After etoposide treatment, the residual minicircle catenanes have a sedimentation coefficient which is only 70% that of controls, and by electron microscopy the networks are less compact. Double-size networks, the characteristic dumbbell-shape forms that normally arise in the final stages of network replication, are replaced by aberrant unit-size forms. 1994-09 2013-07-03T05:26:01Z 2013-07-03T05:26:01Z Journal Article https://hdl.handle.net/10568/33069 en Limited Access Informa UK Limited Molecular and Cellular Biology;14: 5891-5897
spellingShingle trypanosome
dna
mitochondria
animal diseases
cell biology
molecular biology
Shapiro, T.A.
Showalter, F.
In vivo inhibition of trypanosome mitochondrial topoisomerase II: Effects of kinetoplast DNA maxicircles
title In vivo inhibition of trypanosome mitochondrial topoisomerase II: Effects of kinetoplast DNA maxicircles
title_full In vivo inhibition of trypanosome mitochondrial topoisomerase II: Effects of kinetoplast DNA maxicircles
title_fullStr In vivo inhibition of trypanosome mitochondrial topoisomerase II: Effects of kinetoplast DNA maxicircles
title_full_unstemmed In vivo inhibition of trypanosome mitochondrial topoisomerase II: Effects of kinetoplast DNA maxicircles
title_short In vivo inhibition of trypanosome mitochondrial topoisomerase II: Effects of kinetoplast DNA maxicircles
title_sort in vivo inhibition of trypanosome mitochondrial topoisomerase ii effects of kinetoplast dna maxicircles
topic trypanosome
dna
mitochondria
animal diseases
cell biology
molecular biology
url https://hdl.handle.net/10568/33069
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AT showalterf invivoinhibitionoftrypanosomemitochondrialtopoisomeraseiieffectsofkinetoplastdnamaxicircles