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Michele M. Klingbeil - One of the best experts on this subject based on the ideXlab platform.
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orientation of dna minicircles balances density and topological complexity in kinetoplast dna
PLOS ONE, 2015Co-Authors: Yuanan Diao, Michele M. Klingbeil, Victor Rodriguez, Javier ArsuagaAbstract:Kinetoplast DNA (kDNA), a unique mitochondrial structure common to trypanosomatid parasites, contains thousands of DNA minicircles that are densely packed and can be topologically linked into a Chain Mail-like network. Experimental data indicate that every minicircle in the network is, on average, singly linked to three other minicircles (i.e., has mean valence 3) before replication and to six minicircles in the late stages of replication. The biophysical factors that determine the topology of the network and its changes during the cell cycle remain unknown. Using a mathematical modeling approach, we previously showed that volume confinement alone can drive the formation of the network and that it induces a linear relationship between mean valence and minicircle density. Our modeling also predicted a minicircle valence two orders of magnitude greater than that observed in kDNA. To determine the factors that contribute to this discrepancy we systematically analyzed the relationship between the topological properties of the network (i.e., minicircle density and mean valence) and its biophysical properties such as DNA bending, electrostatic repulsion, and minicircle relative position and orientation. Significantly, our results showed that most of the discrepancy between the theoretical and experimental observations can be accounted for by the orientation of the minicircles with volume exclusion due to electrostatic interactions and DNA bending playing smaller roles. Our results are in agreement with the three dimensional kDNA organization model, initially proposed by Delain and Riou, in which minicircles are oriented almost perpendicular to the horizontal plane of the kDNA disk. We suggest that while minicircle confinement drives the formation of kDNA networks, it is minicircle orientation that regulates the topological complexity of the network.
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closing the gaps in kinetoplast dna network replication
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Michele M. KlingbeilAbstract:Trypanosomatids are protozoan parasites responsible for important tropical diseases. One example, Trypanosoma brucei , causes African sleeping sickness, and related parasites cause Chagas disease and leishmaniasis. Because they are among the earliest-branching eukaryotes, trypanosomatids have unusual biological properties. One of their most curious features is a unique mitochondrial DNA network known as kinetoplast DNA (kDNA) (1). The kDNA network is composed of several thousand minicircles that are interlocked like the links in medieval Chain Mail. Also intertwined in the network are a few dozen maxicircles. See Fig. 1 for an electron micrograph of a segment of an isolated kDNA network from Crithidia fasciculata , a trypanosomatid often studied because it is nonpathogenic and easy to cultivate. The function of kDNA maxicircles, like mitochondrial DNA in conventional eukaryotes, is to encode a few gene products such as rRNA and subunits of respiratory complexes. However, the mechanism of gene expression is highly unconventional in that maxicircle transcripts must be edited to form a functional mRNA. Editing is an amazing form of RNA processing in which uridine residues are inserted or deleted at precise internal sites within the maxicircle transcripts, generating ORFs. Minicircles encode guide RNAs that are templates for editing of maxicircle transcripts. See ref. 2 for a review of editing and ref. 3 for a discussion of the evolution of kDNA and the significance of the network structure. Fig. 1. Electron micrograph of a segment of a kDNA network from C. fasciculata . Small loops are minicircles. [Reproduced with permission from ref. 1 (Copyright 2001, Elsevier Science).] In this issue of PNAS, Sinha et al. (4 …
Javier Arsuaga - One of the best experts on this subject based on the ideXlab platform.
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orientation of dna minicircles balances density and topological complexity in kinetoplast dna
PLOS ONE, 2015Co-Authors: Yuanan Diao, Michele M. Klingbeil, Victor Rodriguez, Javier ArsuagaAbstract:Kinetoplast DNA (kDNA), a unique mitochondrial structure common to trypanosomatid parasites, contains thousands of DNA minicircles that are densely packed and can be topologically linked into a Chain Mail-like network. Experimental data indicate that every minicircle in the network is, on average, singly linked to three other minicircles (i.e., has mean valence 3) before replication and to six minicircles in the late stages of replication. The biophysical factors that determine the topology of the network and its changes during the cell cycle remain unknown. Using a mathematical modeling approach, we previously showed that volume confinement alone can drive the formation of the network and that it induces a linear relationship between mean valence and minicircle density. Our modeling also predicted a minicircle valence two orders of magnitude greater than that observed in kDNA. To determine the factors that contribute to this discrepancy we systematically analyzed the relationship between the topological properties of the network (i.e., minicircle density and mean valence) and its biophysical properties such as DNA bending, electrostatic repulsion, and minicircle relative position and orientation. Significantly, our results showed that most of the discrepancy between the theoretical and experimental observations can be accounted for by the orientation of the minicircles with volume exclusion due to electrostatic interactions and DNA bending playing smaller roles. Our results are in agreement with the three dimensional kDNA organization model, initially proposed by Delain and Riou, in which minicircles are oriented almost perpendicular to the horizontal plane of the kDNA disk. We suggest that while minicircle confinement drives the formation of kDNA networks, it is minicircle orientation that regulates the topological complexity of the network.
Paul T. Englund - One of the best experts on this subject based on the ideXlab platform.
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the structure and replication of kinetoplast dna
Annual Review of Microbiology, 1995Co-Authors: Theresa A Shapiro, Paul T. EnglundAbstract:The mitochondrial DNA of trypanosomatid protozoa, termed kinetoplast DNA (kDNA), is unique in its structure, function, and mode of replication. kDNA is a massive network, composed of thousands of topologically interlocked DNA circles, which resembles the Chain Mail of medieval armor. Each cell contains one network condensed into a disk-shaped structure within the matrix of its single mitochondrion. The kDNA circles are of two types, maxicircles present in a few dozen copies and minicircles present in several thousand copies. The maxicircles, which encode ribosomal RNAs and a few mitochondrial proteins, are similar in structure and genetic function to the mitochondrial DNA of other eukaryotes. Many maxicircle transcripts undergo editing, a remarkable process involving the insertion or deletion of uridine residues at specific sites. The minicircles encode small guide RNAs that control the specificity of editing. During kDNA replication, covalently closed minicircles are released from the network by a topoisomerase II. The free minicircles replicate as theta-structures within one of two complexes of replication proteins that are positioned on opposite sides of the kinetoplast disk. The progeny minicircles, which contain nicks or gaps, are attached to the network periphery. Maxicircles also replicate as theta-structures, but they remain linked to the network. As replication proceeds, the number of minicircles and maxicircles increases. When the network has doubled in size, all of the minicircle nicks and gaps are repaired, and the network splits in two. The two progeny networks then segregate into the daughter cells.
Eddy Chukwura Agbo - One of the best experts on this subject based on the ideXlab platform.
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fellowship of the rings the replication of kinetoplast dna
Trends in Parasitology, 2005Co-Authors: Yanan Liu, Shawn A Motyka, Eddy Chukwura AgboAbstract:Kinetoplastid protozoa such as trypanosomes and Leishmania are important because they cause human disease. These parasites are named after one of their most unusual features, a mitochondrial DNA known as kinetoplast DNA (kDNA). Unlike all other DNA in nature, kDNA comprises a giant network of interlocked DNA rings with a topology resembling that of medieval Chain Mail. The replication of the kDNA network is more complex than previously thought, and the discovery of new proteins involved in this process is currently the best approach for illuminating the replication mechanism.
Yuanan Diao - One of the best experts on this subject based on the ideXlab platform.
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orientation of dna minicircles balances density and topological complexity in kinetoplast dna
PLOS ONE, 2015Co-Authors: Yuanan Diao, Michele M. Klingbeil, Victor Rodriguez, Javier ArsuagaAbstract:Kinetoplast DNA (kDNA), a unique mitochondrial structure common to trypanosomatid parasites, contains thousands of DNA minicircles that are densely packed and can be topologically linked into a Chain Mail-like network. Experimental data indicate that every minicircle in the network is, on average, singly linked to three other minicircles (i.e., has mean valence 3) before replication and to six minicircles in the late stages of replication. The biophysical factors that determine the topology of the network and its changes during the cell cycle remain unknown. Using a mathematical modeling approach, we previously showed that volume confinement alone can drive the formation of the network and that it induces a linear relationship between mean valence and minicircle density. Our modeling also predicted a minicircle valence two orders of magnitude greater than that observed in kDNA. To determine the factors that contribute to this discrepancy we systematically analyzed the relationship between the topological properties of the network (i.e., minicircle density and mean valence) and its biophysical properties such as DNA bending, electrostatic repulsion, and minicircle relative position and orientation. Significantly, our results showed that most of the discrepancy between the theoretical and experimental observations can be accounted for by the orientation of the minicircles with volume exclusion due to electrostatic interactions and DNA bending playing smaller roles. Our results are in agreement with the three dimensional kDNA organization model, initially proposed by Delain and Riou, in which minicircles are oriented almost perpendicular to the horizontal plane of the kDNA disk. We suggest that while minicircle confinement drives the formation of kDNA networks, it is minicircle orientation that regulates the topological complexity of the network.