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

M. Di Re, H. Sembongi, J. He, A. Reyes, T. Yasukawa, P. Martinsson, L. J. Bailey, S. Goffart, J. D. Boyd-kirkup, T. S. Wong, A. R. Fersht, J. N. Spelbrink, I. J. Holt

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Abstract

The accessory subunit of mitochondrial DNA polymerase γ, POLGβ, functions as a processivity factor in vitro. Here we show POLGβ 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 POLGβ increased nucleoid numbers, whereas overexpression of POLGβ reduced the number and increased the size of mitochondrial nucleoids. Both increased and decreased expression of POLGβ altered nucleoid structure and precipitated a marked decrease in 7S DNA molecules, which form short displacement-loops on mitochondrial DNA. Recombinant POLGβ preferentially bound to plasmids with a short displacement-loop, in contrast to POLGα. These findings support the view that the mitochondrial D-loop acts as a protein recruitment centre, and suggest POLGβ is a key factor in the organization of mitochondrial DNA in multigenomic nucleoprotein complexes.

Original languageEnglish
Article numbergkp614
Pages (from-to)5701-5713
Number of pages13
JournalNucleic acids research
Volume37
Issue number17
DOIs
Publication statusPublished - Jul 22 2009
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Genetics

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