THE STRUCTURE AND REPLICATION OF KINETOPLAST DNA

The mitochondrial DNA of trypanosomatid protozoa, termed kinetoplast D NA (kDNA), is unique in its structure, function, and mode of replicati on. kDNA is a massive network, composed of thousands of topologically interlocked DNA circles, which resembles the chain mail of medieval ar mor. Each cell contains one network condensed into a disk-shaped struc ture within the matrix of its single mitochondrion. The kDNA circles a re of two types, maxicircles present in a few dozen copies and minicir cles present in several thousand copies. The maxicircles, which encode ribosomal RNAs and a few mitochondrial proteins, are similar in struc ture and genetic function to the mitochondrial DNA of other eukaryotes . Many maxicircle transcripts undergo editing, a remarkable process in volving the insertion or deletion of uridine residues at specific site s. The minicircles encode small guide RNAs that control the specificit y of editing. During kDNA replication, covalently closed minicircles a re released from the network by a topoisomerase II. The free minicircl es replicate as theta-structures within one of two complexes of replic ation proteins that are positioned on opposite sides of the kinetoplas t disk, The progeny minicircles, which contain nicks or gaps, are atta ched to the network periphery. Maxicircles also replicate as theta-str uctures, but they remain linked to the network As replication proceeds , the number of minicircles and maxicircles increases. When the networ k has doubled in size, all of the minicircle nicks and gaps are repair ed, and the network splits in two. The two progeny networks then segre gate into the daughter cells.