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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Di Re, M 
Sembongi, H 
He, J 
Reyes, A 
Yasukawa, T 

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.

Description

Keywords

Cell Line, Tumor, DNA Polymerase gamma, DNA, Mitochondrial, DNA-Directed DNA Polymerase, Humans, Mitochondria, Nucleic Acid Synthesis Inhibitors, Nucleoproteins, Plasmids, Protein Subunits, RNA Interference

Journal Title

Nucleic Acids Res

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

37

Publisher

Oxford University Press (OUP)