New features of mitochondrial DNA replication system in yeast and man

In this review, we sum up the research carried out over two decades on mito chondrial DNA (mtDNA) replication, primarily by comparing this system in Sa ccharomyces cerevisiae and Homo sapiens. Brief incursions into systems of o ther organisms have also been achieved when they provide new information. S. cerevisiae and N. sapiens mitochondrial DNA (mtDNA) have been thought fo r a long time to share closely related architecture and replication mechani sms. However, recent studies suggest that mitochondrial genome of S. cerevi siae may be formed, at least partially, from linear multimeric molecules, w hile human mtDNA is circular. Although several proteins involved in the rep lication of these two genomes are very similar, divergences are also now in creasingly evident. As an example, the recently cloned human mitochondrial DNA polymerase beta-subunit has no counterpart in yeast. Yet, yeast Abf2p a nd human mtTFA are probably not as closely functionally related as thought previously. Some mtDNA metabolism factors, like DNA ligases, were until rec ently largely uncharacterized, and have been found to be derived from alter native nuclear products. Many factors involved in the metabolism of mitocho ndrial DNA are linked through genetic or biochemical interconnections. Thes e links are presented on a may. Finally, we discuss recent studies suggesti ng that the yeast mtDNA replication system diverges from that observed in m an, and may involve recombination, possibly coupled to alternative replicat ion mechanisms like rolling circle replication. (C) 2000 Elsevier Science B .V. All rights reserved.