MITOCHONDRIAL-DNA MAINTENANCE IN VERTEBRATES

The discovery that mutations in mitochondrial DNA (mtDNA) can be patho genic in humans has increased interest in understanding mtDNA maintena nce. The functional state of mtDNA requires a great number of factors for gene expression, DNA replication, and DNA repair. These processes are ultimately controlled by the cell nucleus, because the requisite p roteins are all encoded by nuclear genes and imported into the mitocho ndrion. DNA replication and transcription are linked in vertebrate mit ochondria because RNA transcripts initiated at the light-strand promot er are the primers for mtDNA replication at the heavy-strand origin. S tudy of this transcription-primed DNA replication mechanism has led to isolation of key factors involved in mtDNA replication and transcript ion and to elucidation of unique nucleic acid structures formed at thi s origin. Because features of a transcription-primed mechanism appear to be conserved in vertebrates, a general model for initiation of vert ebrate heavy-strand DNA synthesis is proposed. In many organisms, mtDN A maintenance requires not only faithful mtDNA replication, but also m tDNA repair and recombination. The extent to which these latter two pr ocesses are involved in mtDNA maintenance in vertebrates is also appra ised.