A new function of Trypanosoma brucei mitochondrial topoisomerase II is to maintain kinetoplast DNA network topology

Lindsay, M. E., Gluenz, E. , Gull, K. and Englund, P. T. (2008) A new function of Trypanosoma brucei mitochondrial topoisomerase II is to maintain kinetoplast DNA network topology. Molecular Microbiology, 70(6), pp. 1465-1476. (doi: 10.1111/j.1365-2958.2008.06493.x) (PMID:19019151) (PMCID:PMC2993328)

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The mitochondrial genome of Trypanosoma brucei, called kinetoplast DNA, is a network of topologically interlocked DNA rings including several thousand minicircles and a few dozen maxicircles. Kinetoplast DNA synthesis involves release of minicircles from the network, replication of the free minicircles and reattachment of the progeny. Here we report a new function of the mitochondrial topoisomerase II (TbTOP2mt). Although traditionally thought to reattach minicircle progeny to the network, here we show that it also mends holes in the network created by minicircle release. Network holes are not observed in wild‐type cells, implying that this mending reaction is normally efficient. However, RNAi of TbTOP2mt causes holes to persist and enlarge, leading to network fragmentation. Remarkably, these network fragments remain associated within the mitochondrion, and many appear to be appropriately packed at the local level, even as the overall kinetoplast organization is dramatically altered. The deficiency in mending holes is temporally the earliest observable defect in the complex TbTOP2mt RNAi phenotype.

Item Type:Articles
Additional Information:This work was funded by the National Institutes of Health (Grant AI058613 to P.T.E.) and The Wellcome Trust and EP Abraham Trust (to K.G.). K.G. is a Wellcome Trust Principal Research Fellow.
Glasgow Author(s) Enlighten ID:Gluenz, Dr Eva
Authors: Lindsay, M. E., Gluenz, E., Gull, K., and Englund, P. T.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Molecular Microbiology
ISSN (Online):1365-2958
Published Online:14 October 2008

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