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Lookup NU author(s): Joanna Stewart, Kamil Sitarz, Professor Rita HorvathORCiD, Dr Angela Pyle, Dr Patrick Yu Wai Man, Professor Robert Taylor, Dr David Samuels, Professor Patrick Chinnery
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Disorders of mitochondrial DNA (mtDNA) maintenance have emerged as an important cause of human genetic disease, but demonstrating the functional consequences of de novo mutations remains a major challenge. We studied the rate of depletion and repopulation of mtDNA in human fibroblasts exposed to ethidium bromide in patients with heterozygous POLG mutations. POLG2 and TK2 mutations. Ethidium bromide induced mtDNA depletion occurred at the same rate in human fibroblasts from patients and healthy controls. By contrast, the restoration of mtDNA levels was markedly delayed in fibroblasts from patients with compound heterozygous POLG mutations. Specific POLG2 and TK2 mutations did not delay mtDNA repopulation rates. These observations are consistent with the hypothesis that mutations in POLG impair mtDNA repopulation within intact cells, and provide a potential method of demonstrating the functional consequences of putative pathogenic alleles causing a defect of mtDNA synthesis. (C) 2010 Elsevier B.V. All rights reserved.
Author(s): Stewart JD, Schoeler S, Sitarz KS, Horvath R, Hallmann K, Pyle A, Yu-Wai-Man P, Taylor RW, Samuels DC, Kunz WS, Chinnery PF
Publication type: Article
Publication status: Published
Journal: Biochimica et Biophysica Acta: Molecular Basis of Disease
Year: 2011
Volume: 1812
Issue: 3
Pages: 321-325
Print publication date: 01/03/2011
ISSN (print): 0925-4439
ISSN (electronic): 0006-3002
Publisher: Elsevier BV
URL: http://dx.doi.org/10.1016/j.bbadis.2010.11.012
DOI: 10.1016/j.bbadis.2010.11.012
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