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Article
Subject Categories: Genome Stability & Dynamics
The EMBO Journal (2008) 27, 143–154, doi:10.1038/sj.emboj.7601956
Published online 6 December 2007
p166, a link between the trypanosome mitochondrial DNA and flagellum, mediates genome segregation
Zhixing Zhao1, Megan E Lindsay1, Arnab Roy Chowdhury1, Derrick R Robinson2 and Paul T Englund1
1 Department of Biological Chemistry, Johns Hopkins Medical School, Baltimore, MD, USA
2 Microbiologie Cellulaire et Moléculaire et Pathogénicité, CNRS UMR 5234, Université Bordeaux 2, Bordeaux Cedex, France

To whom correspondence should be addressed
Paul T Englund, Department of Biological Chemistry, Johns Hopkins Medical School, 725 N Wolfe Street, Baltimore, MD 21205, USA. Tel.: +1 410 955 3790; Fax: +1 410 955 7810; E-mail: penglund@jhmi.edu

Received 11 June 2007; Accepted 20 November 2007; Published online 6 December 2007.
Abstract
Kinetoplast DNA (kDNA), the trypanosome mitochondrial genome, is a giant network containing several thousand interlocked DNA rings. Within the mitochondrion, kDNA is condensed into a disk-shaped structure positioned near the flagellar basal body. The disk is linked to the basal body by a remarkable transmembrane filament system named the tripartite attachment complex (TAC). Following kDNA replication, the TAC mediates network segregation, pulling the progeny networks into the daughter cells by their linkage to the basal bodies. So far TAC has been characterized only morphologically with no known protein components. By screening an RNAi library, we discovered p166, a protein localizing between the kDNA and basal body in intact cells and in isolated flagellum–kDNA complexes. RNAi of p166 has only small effects on kDNA replication, but it causes profound defects in network segregation. For example, kDNA replication without segregation causes the networks to grow to enormous size. Thus, p166 is the first reported molecular component of the TAC, and its discovery will facilitate study of kDNA segregation machinery at the molecular level.
Keywords: genome segregation, kinetoplast, mitochondrial DNA, tripartite attachment complex, trypanosome
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