William C Copeland

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi request reprint Mitochondrial genome maintenance in health and disease
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC 27709, USA Electronic address
    DNA Repair (Amst) 19:190-8. 2014
  2. pmc Construction and application of a protein and genetic interaction network (yeast interactome)
    Gregory R Stuart
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences and Life Sciences Division, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 37:e54. 2009
  3. pmc Defects in mitochondrial DNA replication and human disease
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Durham, North Carolina 27709, USA
    Crit Rev Biochem Mol Biol 47:64-74. 2012
  4. pmc Inherited mitochondrial diseases of DNA replication
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Annu Rev Med 59:131-46. 2008
  5. ncbi request reprint DNA polymerase gamma in mitochondrial DNA replication and repair
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P O Box 12233, Research Triangle Park, NC 27709, USA
    ScientificWorldJournal 3:34-44. 2003
  6. ncbi request reprint Mutations in DNA polymerase gamma cause error prone DNA synthesis in human mitochondrial disorders
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Acta Biochim Pol 50:155-67. 2003
  7. ncbi request reprint Mitochondrial DNA alterations in cancer
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P O Box 12233, Research Triangle Park, NC 27709, USA
    Cancer Invest 20:557-69. 2002
  8. ncbi request reprint DNA2 resolves expanding flap in mitochondrial base excision repair
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Mol Cell 32:457-8. 2008
  9. ncbi request reprint The mitochondrial DNA polymerase in health and disease
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
    Subcell Biochem 50:211-22. 2010
  10. pmc Disease mutations in the human mitochondrial DNA polymerase thumb subdomain impart severe defects in mitochondrial DNA replication
    Rajesh Kasiviswanathan
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 284:19501-10. 2009

Collaborators

Detail Information

Publications58

  1. ncbi request reprint Mitochondrial genome maintenance in health and disease
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC 27709, USA Electronic address
    DNA Repair (Amst) 19:190-8. 2014
    ..We briefly review these general elements that affect maintenance of mtDNA, and we focus on nuclear genes encoding the mtDNA replication machinery that can perturb the genetic integrity of the mitochondrial genome. ..
  2. pmc Construction and application of a protein and genetic interaction network (yeast interactome)
    Gregory R Stuart
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences and Life Sciences Division, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 37:e54. 2009
    ....
  3. pmc Defects in mitochondrial DNA replication and human disease
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Durham, North Carolina 27709, USA
    Crit Rev Biochem Mol Biol 47:64-74. 2012
    ..This review focuses on our current knowledge of genetic defects of mtDNA replication (POLG, POLG2, C10orf2) and nucleotide metabolism (TYMP, TK2, DGOUK, and RRM2B) that cause instability of mtDNA and mitochondrial disease...
  4. pmc Inherited mitochondrial diseases of DNA replication
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Annu Rev Med 59:131-46. 2008
    ....
  5. ncbi request reprint DNA polymerase gamma in mitochondrial DNA replication and repair
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P O Box 12233, Research Triangle Park, NC 27709, USA
    ScientificWorldJournal 3:34-44. 2003
    ..The catalytic subunit contains DNA polymerase activity, 3'-5' exonuclease activity, and a 5'-dRP lyase activity. The accessory subunit is required for highly processive DNA synthesis and increases the affinity of pol gamma to the DNA...
  6. ncbi request reprint Mutations in DNA polymerase gamma cause error prone DNA synthesis in human mitochondrial disorders
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Acta Biochim Pol 50:155-67. 2003
    ..The error prone DNA synthesis observed for the Y955C polgamma is consistent with the accumulation of mtDNA mutations in patients with PEO. The effects of other polgamma mutations associated with PEO are discussed...
  7. ncbi request reprint Mitochondrial DNA alterations in cancer
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P O Box 12233, Research Triangle Park, NC 27709, USA
    Cancer Invest 20:557-69. 2002
    ..Mitochondrial DNA mutations can initiate a cascade of events leading to a continuous increase in the production of reactive oxygen species (persistent oxidative stress), a condition that probably favors tumor development...
  8. ncbi request reprint DNA2 resolves expanding flap in mitochondrial base excision repair
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Mol Cell 32:457-8. 2008
    ..2008) demonstrated that human DNA2, originally identified in yeast as a nuclear DNA replication and repair factor, functions exclusively in mammalian mitochondria in the recently discovered long-patch base excision repair pathway...
  9. ncbi request reprint The mitochondrial DNA polymerase in health and disease
    William C Copeland
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Durham, NC 27709, USA
    Subcell Biochem 50:211-22. 2010
    ..Finally, the gene for pol gamma, POLG, is a genetic locus for several mitochondrial disease with over 150 genetic mutations currently identified...
  10. pmc Disease mutations in the human mitochondrial DNA polymerase thumb subdomain impart severe defects in mitochondrial DNA replication
    Rajesh Kasiviswanathan
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 284:19501-10. 2009
    ..To our knowledge this study represents the first structure-function analysis of the thumb subdomain in pol gamma and examines the consequences of mitochondrial disease mutations in this region...
  11. pmc DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations
    Sherine S L Chan
    National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochim Biophys Acta 1787:312-9. 2009
    ..We review the results of these studies, which provide clues to the mechanisms leading to the disease state...
  12. pmc POS5 gene of Saccharomyces cerevisiae encodes a mitochondrial NADH kinase required for stability of mitochondrial DNA
    Micheline K Strand
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Eukaryot Cell 2:809-20. 2003
    ..Thus, the POS5 NADH kinase is required for mitochondrial DNA stability with a critical role in detoxification of reactive oxygen species. These results predict a role for NADH kinase in human mitochondrial diseases...
  13. ncbi request reprint Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia
    Maria A Graziewicz
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    Nat Struct Mol Biol 11:770-6. 2004
    ..The reduced selectivity and catalytic efficiency of the autosomal dominant PEO mutants predict in vivo dysfunction, and the extent of biochemical defects correlates with the clinical severity of the disease...
  14. ncbi request reprint Mitochondrial and nuclear DNA defects in Saccharomyces cerevisiae with mutations in DNA polymerase gamma associated with progressive external ophthalmoplegia
    Gregory R Stuart
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Hum Mol Genet 15:363-74. 2006
    ..The cellular processes contributing to these observations in the mutant yeast cells are potentially relevant to understanding the pathologies observed in human mitochondrial disease patients...
  15. pmc Translesion synthesis past acrolein-derived DNA adducts by human mitochondrial DNA polymerase γ
    Rajesh Kasiviswanathan
    Mitochondrial DNA Replication Group, Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 288:14247-55. 2013
    ..In summary, our data suggest that acrolein-induced exocyclic DNA lesions can be bypassed by mitochondrial DNA polymerase but, in the case of the minor groove γ-HOPdG adduct, at the cost of unprecedented high mutation rates...
  16. pmc Disease variants of the human mitochondrial DNA helicase encoded by C10orf2 differentially alter protein stability, nucleotide hydrolysis, and helicase activity
    Matthew J Longley
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 285:29690-702. 2010
    ..Such partial defects are consistent with the delayed presentation of mitochondrial diseases associated with mutation of C10orf2...
  17. pmc Modulation of the W748S mutation in DNA polymerase gamma by the E1143G polymorphismin mitochondrial disorders
    Sherine S L Chan
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Hum Mol Genet 15:3473-83. 2006
    ..For W748S-E1143G pol gamma, the benefits bestowed by E1143G include increased DNA binding and polymerase activity; however, E1143G was somewhat detrimental to protein stability...
  18. pmc Human mitochondrial DNA polymerase γ exhibits potential for bypass and mutagenesis at UV-induced cyclobutane thymine dimers
    Rajesh Kasiviswanathan
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 287:9222-9. 2012
    ..Our results suggest that T-T usually stalls mitochondrial DNA replication but also suggest a mechanism for the introduction of point mutations and deletions in the mitochondrial genomes of chronically UV-exposed cells...
  19. pmc Nucleotide incorporation by human DNA polymerase gamma opposite benzo[a]pyrene and benzo[c]phenanthrene diol epoxide adducts of deoxyguanosine and deoxyadenosine
    Maria A Graziewicz
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, DHHS, PO Box 12233, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 32:397-405. 2004
    ....
  20. pmc Functional analysis of mutant mitochondrial DNA polymerase proteins involved in human disease
    Sherine S L Chan
    Mitochondrial DNA Replication Group, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
    Methods Mol Biol 554:59-72. 2009
    ..Here we present the protocols to characterize mutant DNA pol gamma proteins, namely, assays for processive DNA synthesis, exonuclease activity, DNA binding, subunit interaction, and protein stability...
  21. pmc Purification and functional characterization of human mitochondrial DNA polymerase gamma harboring disease mutations
    Rajesh Kasiviswanathan
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Methods 51:379-84. 2010
    ....
  22. ncbi request reprint The common A467T mutation in the human mitochondrial DNA polymerase (POLG) compromises catalytic efficiency and interaction with the accessory subunit
    Sherine S L Chan
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 280:31341-6. 2005
    ..We propose that reduced polymerase activity and loss of accessory subunit interaction are responsible for the depletion and deletion of mitochondrial DNA observed in patients with this POLG mutation...
  23. pmc The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine
    Maria A Graziewicz
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Hum Mol Genet 16:2729-39. 2007
    ....
  24. ncbi request reprint DNA polymerase gamma in mitochondrial DNA replication and repair
    Maria A Graziewicz
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA
    Chem Rev 106:383-405. 2006
  25. pmc mip1 containing mutations associated with mitochondrial disease causes mutagenesis and depletion of mtDNA in Saccharomyces cerevisiae
    Jeffrey D Stumpf
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes ofHealth, Research, Triangle Park, NC 27709, USA
    Hum Mol Genet 19:2123-33. 2010
    ....
  26. pmc Transcriptional response to mitochondrial NADH kinase deficiency in Saccharomyces cerevisiae
    Gregory R Stuart
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
    Mitochondrion 9:211-21. 2009
    ..Finally, the pos5Delta expression profile is quite similar to the hap1Delta expression profile previously reported, which may indicate a shared mechanism...
  27. pmc Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia
    Matthew J Longley
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
    Am J Hum Genet 78:1026-34. 2006
    ..The progressive accumulation of mtDNA deletions causes COX deficiency in muscle fibers and results in the clinical phenotype...
  28. ncbi request reprint Mitochondrial toxicity in hearts of CD-1 mice following perinatal exposure to AZT, 3TC, or AZT/3TC in combination
    Sherine S L Chan
    Laboratory of Molecular Genetics, National Institute of Environmental HealthSciences, National Institutes of Health, Research Triangle Park, North Carolina, USA
    Environ Mol Mutagen 48:190-200. 2007
    ..Our data suggest that AZT/3TC combination treatment produces greater mtDNA damage than either agent individually, and that female mice are more sensitive than males to AZT/3TC-induced mtDNA damage...
  29. pmc Clinical and molecular features of POLG-related mitochondrial disease
    Jeffrey D Stumpf
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Cold Spring Harb Perspect Biol 5:a011395. 2013
    ....
  30. pmc De novo mutation in POLG leads to haplotype insufficiency and Alpers syndrome
    Sherine S L Chan
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA
    Mitochondrion 9:340-5. 2009
    ..2157+5_+6 gc-->ag allele, which is likely responsible for the Alpers syndrome phenotype...
  31. ncbi request reprint Preparation of human mitochondrial single-stranded DNA-binding protein
    Matthew J Longley
    Mitochondrial DNA Replication Group, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Query, NC, USA
    Methods Mol Biol 554:73-85. 2009
    ..We show that, similar to E. coli SSB, human mtSSB assembles into a tetramer and binds single-stranded oligonucleotides in a 4-to-1 protein:oligonucleotide molar ratio...
  32. ncbi request reprint Structural determinants in human DNA polymerase gamma account for mitochondrial toxicity from nucleoside analogs
    Susan E Lim
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, P O Box 12233, Research Triangle Park, NC 27709, USA
    J Mol Biol 329:45-57. 2003
    ..Alteration of Glu895 to Ala slightly increased discrimination against dideoxynucleotides and D4T-TP. The mechanisms by which pol gamma selects certain nucleotide analogs are discussed...
  33. pmc Biochemical analysis of human POLG2 variants associated with mitochondrial disease
    Matthew J Young
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, DHHS, Research Triangle Park, NC 27709, USA
    Hum Mol Genet 20:3052-66. 2011
    ....
  34. ncbi request reprint Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis
    Mikhail V Ponamarev
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 277:15225-8. 2002
    ..The error-prone DNA synthesis observed for the Y955C pol gamma is consistent with the accumulation of mtDNA mutations in patients with PEO...
  35. ncbi request reprint Measuring mtDNA mutation rates in Saccharomyces cerevisiae using the mtArg8 assay
    Micheline K Strand
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA
    Methods Mol Biol 197:151-7. 2002
  36. pmc The exonuclease activity of the yeast mitochondrial DNA polymerase γ suppresses mitochondrial DNA deletions between short direct repeats in Saccharomyces cerevisiae
    Jeffrey D Stumpf
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Genetics 194:519-22. 2013
    ....
  37. pmc Polg2 is essential for mammalian embryogenesis and is required for mtDNA maintenance
    Margaret M Humble
    Mitochondrial DNA Replication Group, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA
    Hum Mol Genet 22:1017-25. 2013
    ..Our data indicate that Polg2 function is critical to mammalian embryogenesis and mtDNA replication, and that a single copy of Polg2 is sufficient to sustain life...
  38. pmc Biochemical analysis of the G517V POLG variant reveals wild-type like activity
    Rajesh Kasiviswanathan
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Mitochondrion 11:929-34. 2011
    ..DNA binding by the mutant was also only slightly lower than the wild-type enzyme. Our data suggest that the G517V mutation by itself in pol γ most likely does not have a role in mitochondrial disorders...
  39. ncbi request reprint Consequences of mutations in human DNA polymerase gamma
    Matthew J Longley
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, P O Box 12233, Research Triangle Park, NC 27709, USA
    Gene 354:125-31. 2005
    ..In this paper we review the literature of POLG mutations and discuss their impact on mitochondrial diseases. We also describe a public access web database to annotate POLG mutations for the research community...
  40. pmc Mitochondrial DNA replication and disease: insights from DNA polymerase γ mutations
    Jeffrey D Stumpf
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Cell Mol Life Sci 68:219-33. 2011
    ..This review summarizes the current evidence that identifies and explains disease-causing POLG mutations...
  41. ncbi request reprint Reduction in frataxin causes progressive accumulation of mitochondrial damage
    Gopalakrishnan Karthikeyan
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA
    Hum Mol Genet 12:3331-42. 2003
    ..We conclude that reduced frataxin levels, which is more representative of the disease state, results in considerable oxidative damage in both mitochondrial and nuclear DNA...
  42. ncbi request reprint Purification, separation, and identification of the human mtDNA polymerase with and without its accessory subunit
    Matthew J Longley
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
    Methods Mol Biol 197:245-57. 2002
  43. ncbi request reprint Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome
    Sherine S L Chan
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA
    DNA Repair (Amst) 4:1381-9. 2005
    ..Therefore, the Alpers phenotype in this patient was a consequence of a single-copy gene dose of the A467T allele, and selective elimination of transcripts bearing the E873stop mutation...
  44. pmc Human DNA polymerase theta possesses 5'-dRP lyase activity and functions in single-nucleotide base excision repair in vitro
    Rajendra Prasad
    Laboratory of Structural Biology, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 37:1868-77. 2009
    ..These results are consistent with a role of Pol theta in BER...
  45. pmc The interface of transcription and DNA replication in the mitochondria
    Rajesh Kasiviswanathan
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    Biochim Biophys Acta 1819:970-8. 2012
    ..This article is part of a Special Issue entitled: Mitochondrial Gene Expression...
  46. pmc Ribonucleotide discrimination and reverse transcription by the human mitochondrial DNA polymerase
    Rajesh Kasiviswanathan
    Laboratory of Molecular Genetics, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA
    J Biol Chem 286:31490-500. 2011
    ..The potential biochemical defects of a patient harboring a disease mutation in the same amino acid (E895G) are discussed...
  47. pmc The mitochondrial DNA polymerase as a target of oxidative damage
    Maria A Graziewicz
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, PO Box 12233, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA
    Nucleic Acids Res 30:2817-24. 2002
    ..These results suggest pol gamma as a target of oxidative damage, which may result in a reduction in mitochondrial DNA replication and repair capacities...
  48. pmc DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity
    Shiwei Song
    Department of Biochemistry and Biophysics, Oregon State University, 2011 ALS, Corvallis, OR 97331 7305, USA
    Proc Natl Acad Sci U S A 102:4990-5. 2005
    ....
  49. pmc Long patch base excision repair in mammalian mitochondrial genomes
    Bartosz Szczesny
    Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas 77555, USA
    J Biol Chem 283:26349-56. 2008
    ..The LP-BER activity was marginally affected in FEN-1-depleted mitochondrial extracts, further supporting the involvement of an unidentified 5'-exo/endonuclease in mitochondrial LP-BER...
  50. ncbi request reprint Base composition at mtDNA boundaries suggests a DNA triple helix model for human mitochondrial DNA large-scale rearrangements
    Christophe Rocher
    EMI 99 29 INSERM, Genetique Mitochondriale, Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France
    Mol Genet Metab 76:123-32. 2002
    ..These experiments extend to a DNA polymerase from an eucaryote source the use of a DNA triple helix strand as a primer, like other DNA polymerases from phage and bacterial origins...
  51. pmc Site-specific somatic mitochondrial DNA point mutations in patients with thymidine phosphorylase deficiency
    Yutaka Nishigaki
    Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA
    J Clin Invest 111:1913-21. 2003
    ..We hypothesize that, in patients with TP deficiency, increased levels of dThd and dUrd cause mitochondrial nucleotide pool imbalances, which, in turn, lead to mtDNA abnormalities including site-specific point mutations...
  52. ncbi request reprint Mitochondrial DNA. Methods and protocols. Introduction
    William C Copeland
    Methods Mol Biol 197:v-vi. 2002
  53. pmc Decreased mtDNA, oxidative stress, cardiomyopathy, and death from transgenic cardiac targeted human mutant polymerase gamma
    William Lewis
    Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA
    Lab Invest 87:326-35. 2007
    ..The transgenic model pathophysiologically links human mutant Pol gamma, mtDNA depletion, and mitochondrial oxidative stress to the mtDNA replication apparatus and to CM...
  54. ncbi request reprint Molecular diagnosis of Alpers syndrome
    Khue V Nguyen
    Department of Medicine, University of California, San Diego School of Medicine, 214 Dickinson Street, Bldg CTF, Rm C 103, San Diego, CA 92103 8467, USA
    J Hepatol 45:108-16. 2006
    ..Mutations in the gene for the mitochondrial DNA polymerase (POLG) have recently been shown to cause this disorder...
  55. pmc Progressive external ophthalmoplegia and vision and hearing loss in a patient with mutations in POLG2 and OPA1
    Silvio Ferraris
    Department of Pediatrics, University of Turin, Turin, Italy
    Arch Neurol 65:125-31. 2008
    ..To describe the clinical features, muscle pathological characteristics, and molecular studies of a patient with a mutation in the gene encoding the accessory subunit (p55) of polymerase gamma (POLG2) and a mutation in the OPA1 gene...
  56. pmc Oxidative stress-induced apoptosis in neurons correlates with mitochondrial DNA base excision repair pathway imbalance
    Jason F Harrison
    Department of Cell Biology and Neuroscience, University of South Alabama, Mobile, AL 36688, USA
    Nucleic Acids Res 33:4660-71. 2005
    ..This study provides evidence linking neuronal mtDNA repair capacity with oxidative stress-related neurodegeneration...
  57. pmc Antiretroviral nucleosides, deoxynucleotide carrier and mitochondrial DNA: evidence supporting the DNA pol gamma hypothesis
    William Lewis
    Department of Pathology, Emory University, Atlanta, Georgia 30322, USA
    AIDS 20:675-84. 2006
    ..Transgenic mice (TG) expressing human DNC targeted to murine myocardium served to define mitochondrial events from NRTIs in vivo and findings were corroborated by biochemical events in vitro...
  58. ncbi request reprint Origins of human mitochondrial point mutations as DNA polymerase gamma-mediated errors
    Weiming Zheng
    Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, 02139, USA
    Mutat Res 599:11-20. 2006
    ..For the sequence studied, these data support the conclusion that, endogenous error mediated by DNA pol gamma constitutes the primary source of mitochondrial point mutations in human tissues...