Priming of human mitochondrial DNA replication occurs at the light-strand promoter.

Publisher Website
Google Scholar
Abstract
Individual promoters for transcription of each strand of human mtDNA are located near the origin of heavy-strand DNA replication in the displacement-loop region. Initiation of heavy-strand synthesis represents the first event in mtDNA replication. Analyses of the 59 and 39 map positions of displacement-loop nucleic acids from mitochondria of cultured human cells reveal a close correspondence between the 39 ends of RNA, whose 59 ends map at a unique site, and the 59 ends of DNA strands. The 59 ends of the RNA species all map at nucleotide position 407 in the genomic sequence, which corresponds exactly to the major 59 transcriptional start site, determined previously in vitro, that is contained within the light-strand promoter sequence. Displacement-loop heavy-strand DNAs map immediately adjacent to the 39 termini of these RNAs, and these transition points between RNA and DNA lie within short conserved sequence blocks in the template sequence. The simplest interpretation of these data is that replication is initiated at the major transcriptional promoter with subsequent precise cleavage of primary transcripts to provide the appropriate primer species.