Unraveling the Secrets of Regulating Mitochondrial DNA Replication

Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA.
Molecular cell (Impact Factor: 14.02). 09/2009; 35(4):398-400. DOI: 10.1016/j.molcel.2009.08.007
Source: PubMed


In this issue, Liu et al. (2009) report that maxicircle DNA copy number in trypanosomes is regulated by proteolysis of a helicase; the complex kinetoplast DNA system yields a clear view of how mitochondrial DNA replication can be regulated.

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Available from: Michele Klingbeil
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    • "It apparently occurs concurrently with the repositioning of the newly formed basal body (Gluenz et al., 2011). Regulation of kinetoplast replication is under tight control in a manner that is reminiscent of the nuclear DNA replication licensing system (Klingbeil and Shapiro, 2009;Li et al., 2008b;Liu et al., 2009). A mitochondrial HslVU protease, a eubacterial counterpart of the eukaryotic 26S proteasome, plays an essential role in preventing kinetoplast rereplication, thus maintaining the copy number of both the minicircle and maxicircle DNA in the kinetoplast (Li et al., 2008b). "
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    ABSTRACT: The cell division cycle is tightly regulated by the activation and inactivation of a series of proteins that control the replication and segregation of organelles to the daughter cells. During the past decade, we have witnessed significant advances in our understanding of the cell cycle in Trypanosoma brucei and how the cycle is regulated by various regulatory proteins. However, many other regulators, especially those unique to trypanosomes, remain to be identified, and we are just beginning to delineate the signaling pathways that drive the transitions through different cell cycle stages, such as the G(1)/S transition, G(2)/M transition, and mitosis-cytokinesis transition. Trypanosomes appear to employ both evolutionarily conserved and trypanosome-specific molecules to regulate the various stages of its cell cycle, including DNA replication initiation, spindle assembly, chromosome segregation, and cytokinesis initiation and completion. Strikingly, trypanosomes lack some crucial regulators that are well conserved across evolution, such as Cdc6 and Cdt1, which are involved in DNA replication licensing, the spindle motor kinesin-5, which is required for spindle assembly, the central spindlin complex, which has been implicated in cytokinesis initiation, and the actomyosin contractile ring, which is located at the cleavage furrow. Conversely, trypanosomes possess certain regulators, such as cyclins, cyclin-dependent kinases, and mitotic centromere-associated kinesins, that are greatly expanded and likely play diverse cellular functions. Overall, trypanosomes apparently have integrated unique regulators into the evolutionarily conserved pathways to compensate for the absence of those conserved molecules and, additionally, have evolved certain cell cycle regulatory pathways that are either different from its human host or distinct between its own life cycle forms.
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