Both heavy strand replication origins are active in partially duplicated human mitochondrial DNAs

Shuyo Umeda, Yingying Tang, Mayumi Okamoto, Naotaka Hamasaki, Eric A. Schon, Dongchon Kang

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

The replication of human mitochondrial DNA (mtDNA) is initiated from a pair of displaced origins, one priming continuous synthesis of daughter-strand DNA from the heavy strand (OH) and the other priming continuous synthesis from the light strand (OL). In patients with sporadic large-scale rearrangements of mitochondrial DNA (i.e., partially.deleted [Δ-mtDNA] and partially-duplicated [dup-mtDNA] molecules), the dup-mtDNAs typically contain extra origins of replication, but it is unknown at present whether they are competent for initiation of replication. Using cybrids harboring each of two types of dup-mtDNAs - One containing two OHs and two OLs, and one containing two OHs and one OL - We used ligation-mediated polymerase chain reaction (LMPCR) to measure the presence and relative amounts of nascent heavy strands originating from each OH. We found that the nascent heavy strands originated almost equally from the two OHs in each cell line, indicating that the extra OH present on a partially duplicated mtDNA is competent for heavy strand synthesis. This extra OH could potentially confer a replicative advantage to dup-mtDNAs, as these molecules may have twice as many opportunities to initiate replication compared to wild-type (or partially deleted) molecules.

Original languageEnglish
Pages (from-to)681-687
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume286
Issue number4
DOIs
Publication statusPublished - 2001

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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