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The accessory subunit B of DNA polymerase gamma is required for mitochondrial replisome function.

Journal article
Authors Géraldine Farge
Xuan Hoi Pham
Teresa Holmlund
Ivan Khorostov
Maria Falkenberg
Published in Nucleic acids research
Volume 35
Issue 3
Pages 902-11
ISSN 1362-4962
Publication year 2007
Published at
Pages 902-11
Language en
Keywords DNA, metabolism, DNA Helicases, genetics, metabolism, DNA Replication, DNA, Mitochondrial, biosynthesis, DNA, Single-Stranded, metabolism, DNA-Directed DNA Polymerase, genetics, metabolism, physiology, Humans, Multienzyme Complexes, metabolism, Mutation, Protein Subunits, genetics, metabolism, physiology, Templates, Genetic
Subject categories Chemistry

Abstract

The mitochondrial replication machinery in human cells includes the DNA polymerase gamma holoenzyme and the TWINKLE helicase. Together, these two factors form a processive replication machinery, a replisome, which can use duplex DNA as template to synthesize long stretches of single-stranded DNA. We here address the importance of the smaller, accessory B subunit of DNA polymerase gamma and demonstrate that this subunit is absolutely required for replisome function. The duplex DNA binding activity of the B subunit is needed for coordination of POLgamma holoenzyme and TWINKLE helicase activities at the mtDNA replication fork. In the absence of proof for direct physical interactions between the components of the mitochondrial replisome, these functional interactions may explain the strict interdependence of TWINKLE and DNA polymerase gamma for mitochondrial DNA synthesis. Furthermore, mutations in TWINKLE as well as in the catalytic A and accessory B subunits of the POLgamma holoenzyme, may cause autosomal dominant progressive external ophthalmoplegia, a disorder associated with deletions in mitochondrial DNA. The crucial importance of the B subunit for replisome function may help to explain why mutations in these three proteins cause an identical syndrome.

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