THE STRUCTURE AND REPLICATION OF KINETOPLAST DNA

Abstract

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.