Unique Characteristics of the Kinetoplast DNA Replication Machinery Provide Potential Drug Targets in Trypanosomatids

Kinetoplast DNA (kDNA) is a remarkable DNA structure found in the single mitohondrion of flagellated protozoa of the order Kinetoplastida. In various parasitic species of the family Trypanosomatidae, it consists of 5,000-10,000 duplex DNA minicircles (0.5-10 kb) and 25-50 maxicircles (20-40 kb), which are linked topologically into a two dimensional DNA network. Maxicircles encode for typical mitochondrial proteins and ribosomal RNA, whereas minicircles encode for guide RNA (gRNA) molecules that function in the editing of maxicircles’ mRNA transcripts. The replication of kDNA includes the duplication of free detached minicircles and catenated maxicircles, and the generation of two progeny kDNA networks. It is catalyzed by an enzymatic machinery, consisting of kDNA replication proteins that are located at defined sites flanking the kDNA disk in the mitochondrial matrix (for recent reviews on kDNA see refs. 1-8).