39 Mitochondrial DNA Replication

Abstract

Eukaryotic mitochondrial organelles contain a genome separate and distinct from that of the nucleus. Although limited in genetic content, expression of mitochondrial DNA (mtDNA) is an essential function in most eukaryotes, and therefore the genome is not dispensable. Strategies designed to define both cis-acting elements and trans-acting factors required for mtDNA replication have been developed over the last 25 years. Both in vivo and in vitro approaches have been employed to describe the mode of mammalian mtDNA replication. This chapter first reviews the basics of earlier works and then turns to more recent investigations that focus on early steps in the replication process. Finally, comparison is made to yeast mtDNAs. The novel kinetoplast DNA is reviewed by Torri et al. (this volume).

BASIC BACKGROUND
Although mtDNA comprises typically less than 1% of a metazoan cell’s DNA population, the cellular copy number is 10³ to 10⁴, given the relatively small size of these genomes (~16 kb). It is usually assumed that mtDNA is present in several copies per mitochondrion, but the organelle population is likely dynamic in the living cell, and the distribution of mtDNA may therefore be variable. Replication is under relaxed control and there is no apparent accounting of DNA origins that ensures that each molecule is replicated once and only once per cell cycle, a requirement assumed to be strictly enforced in the case of chromosomal DNA origins of replication. Consistent with this is the lack of any sharp restriction on mtDNA replication with regard to cell cycle...