Mammalian mitochondrial DNA replication is initiated by the processing of RNA transcripts derived from an upstream promoter to create RNA primers for DNA replication. In the yeast Saccharomyces cerevisiae, mitochondrial ori/rep sequences contain a transcription promoter upstream of the site of transition from RNA to DNA synthesis, suggesting a common mode of replication initiation. Recent research has identified features in the mode and machinery of DNA replication conserved from yeast to mammals.