Nucleic Acids Research Advance Access originally published online on January 23, 2007
Nucleic Acids Research 2007 35(3):902-911; doi:10.1093/nar/gkl1116
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Nucleic Acids Research, 2007, Vol. 35, No. 3 902-911
© 2007 The Author(s).
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Nucleic Acid Enzymes |
The accessory subunit B of DNA polymerase 
is required for mitochondrial replisome function
Division of Metabolic Diseases, Karolinska Institutet, Novum, SE-141 86 Stockholm, Sweden
*To whom correspondence should be addressed. Tel: +46 8 58583730; Fax: +46 8 779 5383; E-mail: maria.falkenberg{at}ki.se
Received October 9, 2006. Revised November 16, 2006. Accepted December 6, 2006.
The mitochondrial replication machinery in human cells includes the DNA polymerase 
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 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 POL 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 for mitochondrial DNA synthesis. Furthermore, mutations in TWINKLE as well as in the catalytic A and accessory B subunits of the POL 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.