The accessory subunit of mitochondrial DNA polymerase gamma determines the DNA content of mitochondrial nucleoids in human cultured cells.

TitleThe accessory subunit of mitochondrial DNA polymerase gamma determines the DNA content of mitochondrial nucleoids in human cultured cells.
Publication TypeJournal Article
Year of Publication2009
AuthorsDi Re, M, Sembongi, H, He, J, Reyes, A, Yasukawa, T, Martinsson, P, Bailey, LJ, Goffart, S, Boyd-Kirkup, JD, Wong, TS, Fersht, AR, Spelbrink, JN, Holt, IJ
JournalNucleic Acids Res
Volume37
Issue17
Pagination5701-13
Date Published2009 Sep
ISSN1362-4962
KeywordsCell Line, Tumor, DNA Polymerase gamma, DNA, Mitochondrial, DNA-Directed DNA Polymerase, Humans, Mitochondria, Nucleic Acid Synthesis Inhibitors, Nucleoproteins, Plasmids, Protein Subunits, RNA Interference
Abstract

The accessory subunit of mitochondrial DNA polymerase gamma, POLGbeta, functions as a processivity factor in vitro. Here we show POLGbeta has additional roles in mitochondrial DNA metabolism. Mitochondrial DNA is arranged in nucleoprotein complexes, or nucleoids, which often contain multiple copies of the mitochondrial genome. Gene-silencing of POLGbeta increased nucleoid numbers, whereas over-expression of POLGbeta reduced the number and increased the size of mitochondrial nucleoids. Both increased and decreased expression of POLGbeta altered nucleoid structure and precipitated a marked decrease in 7S DNA molecules, which form short displacement-loops on mitochondrial DNA. Recombinant POLGbeta preferentially bound to plasmids with a short displacement-loop, in contrast to POLGalpha. These findings support the view that the mitochondrial D-loop acts as a protein recruitment centre, and suggest POLGbeta is a key factor in the organization of mitochondrial DNA in multigenomic nucleoprotein complexes.

DOI10.1093/nar/gkp614
Alternate JournalNucleic Acids Res.
Citation Key10.1093/nar/gkp614
PubMed ID19625489
PubMed Central IDPMC2761280
Grant ListMC_U105474168 / / Medical Research Council / United Kingdom
MC_U105663140 / / Medical Research Council / United Kingdom