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J. Biol. Chem., Vol. 278, Issue 51, 50961-50969, December 19, 2003
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From the aDunn Human Nutrition Unit, Wellcome Trust-Medical Research Council Building, Hills Road, Cambridge CB2 2XY, United Kingdom, the dSezione di Bioinformatica e Genomica di Bari, Istituto Tecnologie Biomediche, Consiglio Nazionale delle Ricerche, Via Amendola 168/5, 70126 Bari, Italy, the fInstitute of Medical Technology and Tampere University Hospital, FIN-33014, University of Tampere, Finland and the Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom, and the iDepartment of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, New York 14263-0001
Previous data from our laboratory suggested that replication of mammalian mitochondrial DNA initiates exclusively at or near to the formerly designated origin of heavy strand replication, OH, and proceeds unidirectionally from that locus. New results obtained using two-dimensional agarose gel electrophoresis of replication intermediates demonstrate that replication of mitochondrial DNA initiates from multiple origins across a broad zone. After fork arrest near OH, replication is restricted to one direction only. The initiation zone of bidirectional replication includes the genes for cytochrome b and NADH dehydrogenase subunits 5 and 6.
Received for publication, July 23, 2003 , and in revised form, September 5, 2003.
* The United Kingdom Medical Research Council provided financial support for this work. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains Supplementary Data Figs. 1-4.
b These authors contributed equally to this study.
c Holder of an overseas fellowship from the Japanese Society for the Promotion of Science.
e Recipient of a Royal Society visiting fellowship.
g Supported by the Academy of Finland and Tampere University Hospital Medical Research Fund.
h The collaboration between these two authors is supported by European Union Project MitEURO Grant QLG1-CT-2001-00966.
j Supported by National Institutes of Health Grants GM49294, CA95908, and CA84302.
k To whom correspondence should be addressed. Tel.: 44-1223-252840; Fax: 44-1223-252845. E-mail: holt{at}mrc-dunn.cam.ac.uk.
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