Fellowship of the rings: the replication of kinetoplast DNA

Liu, Beiyu; Liu, Yanan; Motyka, Shawn A.; Agbo, E.E.C.; Englund, Paul T.

doi:10.1016/j.pt.2005.06.008

Cited by 226 publications

(225 citation statements)

References 59 publications

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“…RNA editing and kDNA replication are baroque processes, requiring dozens to hundreds of proteins (2,3,5). However, it is the unfaithful replication and/or segregation of minicircles that is the trigger of kDNA loss.…”

Section: Discussionmentioning

confidence: 99%

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Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei

Lai

Hashimi

Lun

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

243

207

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Section: Discussionmentioning

confidence: 99%

“…A sophisticated machinery ensures faithful replication of the kDNA of T. brucei, which is represented by thousands of minicircles (each Ϸ1.0 kb in size) and dozens of maxicircles (Ϸ23 kb) (4,5). Because it supplies the substrate gRNAs required for RNA editing, the possibility that T. brucei would lose its kDNA would seem unlikely.…”

mentioning

confidence: 99%

Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei

Lai

Hashimi

Lun

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

243

207

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“…Understanding the mechanism of kinetoplast DNA (kDNA) replication has been of great interest [1,2]. Initiation of kDNA and nuclear DNA (nDNA) replication probably coincide, but kDNA segregation is completed before the onset of mitosis [3].…”

Section: Introductionmentioning

confidence: 99%

Analysis of the Trypanosoma brucei cell cycle by quantitative DAPI imaging

Siegel

Hekstra

Cross

2008

Molecular and Biochemical Parasitology

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Trypanosoma brucei has two DNA compartments: the nucleus and the kinetoplast. DNA replication of these two compartments only partially coincides. Woodward and Gull [J Cell Sci 1990;95:49-57] comprehensively studied the relative timing of the replication and segregation of nuclear and kinetoplast DNA. Others have since assumed the consistency of morphological indicators of cellcycle stage among strains and conditions. We report the use of quantitative DAPI imaging to determine the cell-cycle stage of individual procyclic cells. Using this approach, we found that kinetoplast elongation occurs mainly during nuclear S phase and not during G2, as previously assumed. We confirmed this finding by sorting cells by DNA content, followed by fluorescence microscopy. In addition, simultaneous quantitative imaging at two wavelengths can be used to determine the abundance of cell-cycle-regulated proteins during the cell cycle. We demonstrate this technique by co-staining for the non-acetylated state of lysine 4 of histone H4 (H4K4), which is enriched during nuclear S phase. KeywordsCell cycle; Deconvolution microscopy; DNA quantification; Fluorescence-activated cell sorting; Histone modification; Trypanosoma brucei Members of the order Kinetoplastidae are characterized by the presence of the kinetoplast, the uniquely structured mitochondrial DNA that consists of an interlocked network of several thousand minicircles and more than twenty maxicircles. Understanding the mechanism of kinetoplast DNA (kDNA) replication has been of great interest [1,2]. Initiation of kDNA and nuclear DNA (nDNA) replication probably coincide, but kDNA segregation is completed before the onset of mitosis [3]. Any cell can hence be assigned to a specific cell-cycle stage by comparing nuclear and kinetoplast morphology. For example, cells with an elongated kinetoplast would be in the G2. However, our recent studies suggested that elongated kinetoplasts exist in nuclear S phase as well as [4].The goal of this study was to determine the cell-cycle stage of individual cells solely by their nDNA content. Using modern fluorescence microscopy and deconvolution algorithms, we * Corresponding author. Tel.: +1 212 327 7571; fax: +1 212 327 7845. E-mail address: george.cross@rockefeller.edu (G.A.M. Cross). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Quantification of images requires images of high quality. Spherical aberration, nonuniform illumination, and differential response of sensor pixels, need to be avoided or corrected for. Spherical aberration occurs when light waves passing through the periphery of...

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“…The kinetoplast DNA (kDNA) has been shown by fluorescence microscopy studies to be the favored binding site of the compounds [22]. The kDNA is one of the most unusual nucleic acid structures found in any organism [26][27][28]. In T. brucei, the cause of sleeping sickness, the structure consists of approximately 50 DNA maxicircles of 20000-40000 base pairs.…”

Section: Introductionmentioning

confidence: 99%

Sequence and length dependent thermodynamic differences in heterocyclic diamidine interactions at AT base pairs in the DNA minor groove

Liu

Kumar

Boykin

et al. 2007

Biophysical Chemistry

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With the goal of developing a better understanding of the antiparasitic biological action of DB75, we have evaluated its interaction with duplex alternating and nonalternating sequence AT polymers and oligomers. These DNAs provide an important pair of sequences in a detailed thermodynamic analysis of variations in interaction of DB75 with AT sites. The results for DB75 binding to the alternating and nonalternating AT sequences are quite different at the fundamental thermodynamic level. Although the Gibbs energies are similar, the enthalpies for DB75 binding with poly(dA)·poly (dT) and poly(dA-dT)·poly(dA-dT) are +3.1 and −4.5 kcal/mole, respectively, while the binding entropies are 41.7 and 15.2 cal/mol·K, respectively. The underlying thermodynamics of binding to AT sites in the minor groove plays a key role in the recognition process. It was also observed that DB75 binding with poly(dA)·poly(dT) can induce T·A·T triplet formation and the compound binds strongly to the dT·dA·dT triplex.

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Fellowship of the rings: the replication of kinetoplast DNA

Cited by 226 publications

References 59 publications

Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei

Adaptations of Trypanosoma brucei to gradual loss of kinetoplast DNA: Trypanosoma equiperdum and Trypanosoma evansi are petite mutants of T. brucei

Analysis of the Trypanosoma brucei cell cycle by quantitative DAPI imaging

Sequence and length dependent thermodynamic differences in heterocyclic diamidine interactions at AT base pairs in the DNA minor groove

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