- Email: [email protected]
Kinetoplast DNA
MITOCHONDRIAL DNA
BIOLOGY IN PICTURES
Kincetoplast DNA Ainetoplast DNA is the mitochondrial DNA of the parasitic protozoa Try~anosoma, Leishmania and Crithidia. In its structure, replication mechanism and genetic function, it is one of the most amazing DNAs in nature.
In this electron micrograph (EM) of isolated Crithidia fusciculata kinetoplast DNA &DNA), it is shown as a network organized like chain mail, containing several thousand interlocked DNA minicircles and a few dozen maxicircles. The isolated network is an elliptical sheet about 10 pm by 15 urn in size. Inside the cells single mitochondrion the kDNA is condensed into a disk, about 1 urn in diameter and 0.3 urn thick, which is situated between two complexes of replication proteins (including DNA polymerase, topoisomerase II and other enzymes). HQWdoes the network replicate? Minicircles are released from the network center, probably by a second topoisomerase II, and migrate to one of the tvvo complexes where they undergo replication. The minicircle progeny, after release from the complexes, are.reattached to the network periphery. To ensure a uniform distribution of newly synthesized circles around the network periphery, the kinetoplast disk probably rotates between the two complexes, making one turn about every 12 minutes. During each S phase, which is 60-90 minutes for C fmiculata, all of the parental minicircles are released, replicated and their progeny reattached, resulting in a double size network. This splits in two and the progeny networks, each identical to the parent, segregate into the daughter cells. kDNA has a remarkable genetic function. Maxicircles resemble conventional mitochondrial DNAs as they encode rRNA.sand proteins such of cytochrome oxidase and NADH dehydrogenase. However, to function as mI?NAs, the transcripts must first be edited by adding or deleting uridine residues. Editing must be precise, as it occurs within the coding region. For some genes, editing changes as much as 50 % of the coding sequence of the transcript. How does editing work? Short ,guide RNAs, encoded either by the maxicircles or the minicircles, control the specificity of the process by pairing with the maxicircle transcript. U&lines in a tail at the 3’ end of the guide RNA are transferred to the editing site, possibly in a transesterilication reaction. The trypanosome’s kDNA, with its unusual structure, replication mechanism and processing of its transcripts, has been a continuing source of surprises. Perhaps some unusual proper& of kDNA could eventually lead to the parasite’s downfall. It could be a target for selective chemotherapy, helping to eradicate some of the diseases caused by these parasites. EM and text kindly provided by David Perez-Morga and Paul T. Englund, Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205.2185, USA
@
Current
Biology
1993,
Vol
3 No
8
529
BIOLOGY IN PICTURES
Kincetoplast DNA Ainetoplast DNA is the mitochondrial DNA of the parasitic protozoa Try~anosoma, Leishmania and Crithidia. In its structure, replication mechanism and genetic function, it is one of the most amazing DNAs in nature.
In this electron micrograph (EM) of isolated Crithidia fusciculata kinetoplast DNA &DNA), it is shown as a network organized like chain mail, containing several thousand interlocked DNA minicircles and a few dozen maxicircles. The isolated network is an elliptical sheet about 10 pm by 15 urn in size. Inside the cells single mitochondrion the kDNA is condensed into a disk, about 1 urn in diameter and 0.3 urn thick, which is situated between two complexes of replication proteins (including DNA polymerase, topoisomerase II and other enzymes). HQWdoes the network replicate? Minicircles are released from the network center, probably by a second topoisomerase II, and migrate to one of the tvvo complexes where they undergo replication. The minicircle progeny, after release from the complexes, are.reattached to the network periphery. To ensure a uniform distribution of newly synthesized circles around the network periphery, the kinetoplast disk probably rotates between the two complexes, making one turn about every 12 minutes. During each S phase, which is 60-90 minutes for C fmiculata, all of the parental minicircles are released, replicated and their progeny reattached, resulting in a double size network. This splits in two and the progeny networks, each identical to the parent, segregate into the daughter cells. kDNA has a remarkable genetic function. Maxicircles resemble conventional mitochondrial DNAs as they encode rRNA.sand proteins such of cytochrome oxidase and NADH dehydrogenase. However, to function as mI?NAs, the transcripts must first be edited by adding or deleting uridine residues. Editing must be precise, as it occurs within the coding region. For some genes, editing changes as much as 50 % of the coding sequence of the transcript. How does editing work? Short ,guide RNAs, encoded either by the maxicircles or the minicircles, control the specificity of the process by pairing with the maxicircle transcript. U&lines in a tail at the 3’ end of the guide RNA are transferred to the editing site, possibly in a transesterilication reaction. The trypanosome’s kDNA, with its unusual structure, replication mechanism and processing of its transcripts, has been a continuing source of surprises. Perhaps some unusual proper& of kDNA could eventually lead to the parasite’s downfall. It could be a target for selective chemotherapy, helping to eradicate some of the diseases caused by these parasites. EM and text kindly provided by David Perez-Morga and Paul T. Englund, Department of Biological Chemistry, Johns Hopkins University, Baltimore, Maryland 21205.2185, USA
@
Current
Biology
1993,
Vol
3 No
8
529