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Your Environment. Your Health.

Selected Publications

Mitochondrial DNA Replication Group

  1. Young MJ, Copeland WC. Human mitochondrial DNA replication machinery and disease. Current opinion in genetics & development 2016 38():52-62. [Abstract]
  2. DeBalsi KL, Hoff KE, Copeland WC. Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases. Ageing research reviews 2016 Apr 30. pii: S1568-1637(16)30059-9. [Abstract]
  3. Young MJ, Humble MM, DeBalsi KL, Sun KY, Copeland WC. POLG2 disease variants: analyses reveal a dominant negative heterodimer, altered mitochondrial localization and impaired respiratory capacity. Human molecular genetics 2015 24(18):5184-5197. [Abstract]
  4. Shaughnessy DT1, McAllister K, Worth L, Haugen AC, Meyer JN, Domann FE, Van Houten B, Mostoslavsky R, Bultman SJ, Baccarelli AA, Begley TJ, Sobol RW, Hirschey MD, Ideker T, Santos JH, Copeland WC, Tice RR, Balshaw DM, Tyson FL. Mitochondria, energetics, epigenetics, and cellular responses to stress. Environmental Health Perspectives 2014 122(12):1271-1278. [Abstract]
  5. Stumpf JD, Copeland WC. (2014)  MMS Exposure Promotes Increased MtDNA Mutagenesis in the Presence of Replication-Defective Disease-Associated DNA Polymerase γ Variants PLoS genetics 10(10):e1004748-.  [Abstract]
  6. Copeland WC, Longley MJ. Mitochondrial genome maintenance in health and disease. DNA repair 2014 19(July 2014):190-198. [Abstract]
  7. Stumpf JD, Copeland WC. (2013) The Exonuclease Activity of the Yeast Mitochondrial DNA Polymerase γ Suppresses Mitochondrial DNA Deletions Between Short Direct Repeats in Saccharomyces cerevisiae. Genetics 194(2):519-522. [Abstract]
  8. Kasiviswanathan R, Minko IG, Lloyd RS, Copeland WC. (2013) Translesion Synthesis Past Acrolein-derived DNA Adducts by Human Mitochondrial DNA Polymerase γ. The Journal of Biological Chemistry 288(20):14247-14255. [Abstract]
  9. Humble MM, Young MJ, Foley JF, Pandiri AR, Travlos GS, Copeland WC. 2013. Polg2 is essential for mammalian embryogenesis and is required for mtDNA maintenance. Human molecular genetics. 22(5):1017-1025.  [Abstract]
  10. Sohl C.D., Kasiviswanathan R., Copeland W.C., Anderson K.S. (2013) Mutations in human DNA polymerase γ confer unique mechanisms of catalytic deficiency that mirror the disease severity in mitochondrial disorder patients. Human molecular genetics 15(22):1074-1085. [Abstract]
  11. Sohl CD, Kasiviswanathan R, Kim J, Pradere U, Schinazi RF, Copeland WC, Mitsuya H, Baba M, Anderson KS. (2012) Balancing antiviral potency and host toxicity: identifying a nucleotide inhibitor with an optimal kinetic phenotype for HIV-1 reverse transcriptase. Molecular pharmacology 82(1):125-33. [Abstract]
  12. Kasiviswanathan R, Gustafson MA, Copeland WC, Meyer JN. (2012) Human mitochondrial DNA polymerase γ exhibits potential for bypass and mutagenesis at UV-induced cyclobutane thymine dimers. The Journal of biological chemistry. 287(12):9222-9. [Abstract]
  13. Sohl CD, Singh K, Kasiviswanathan R, Copeland WC, Mitsuya H, Sarafianos SG, Anderson KS. (2012) Mechanism of interaction of human mitochondrial DNA polymerase γ with the novel nucleoside reverse transcriptase inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine indicates a low potential for host toxicity. Antimicrobial agents and chemotherapy.  56(3):1630-4. [Abstract]
  14. Craig K, Young MJ, Blakely EL, Longley MJ, Turnbull DM, Copeland WC, Taylor RW. (2012) A p.R369G POLG2 mutation associated with adPEO and multiple mtDNA deletions causes decreased affinity between polymerase γ subunits. Mitochondrion 12(2):313-9. [Abstract]
  15. Kasiviswanathan R, Collins TR, Copeland WC. (2012) The interface of transcription and DNA replication in the mitochondria. Biochimica et biophysica acta 1819(9-10):970-8. [Abstract]
  16. Kasiviswanathan, R., and Copeland, W.C. (2011) Biochemical analysis of the G517V POLG variant reveals wild-type like activity. Mitochondrion  11(6):929-934. [Abstract]
  17. Kasiviswanathan, R., and Copeland, W.C. (2011) Ribonucleotide discrimination and reverse transcription by the human mitochondrial DNA polymerase. The Journal of biological chemistry 286(36):31490-314500. [Abstract]
  18. Young, M.J., Longley, M.J., Li, F., Kasiviswanathan, R., Wong, L.J., Copeland, W.C. (2011) Biochemical analysis of human POLG2 variants associated with mitochondrial disease. Human molecular genetics 20(15):3052-3066. [Abstract]
  19. Stumpf, J.D., Copeland, W.C. (2011) Mitochondrial DNA Replication and Disease: Insights from DNA Polymerase [gamma] Mutations. Cellular and molecular life sciences 68(2):219-233. [Abstract]
  20. Longley, M.J., Humble, M.M., Sharief, F.S., Copeland, W.C. (2010) Disease Variants of the Human Mitochondrial DNA Helicase Encoded by C10orf2 Differentially Alter Protein Stability, Nucleotide Hydrolysis and Helicase Activity. The Journal of biological chemistry 285(39):29690-296702. [Abstract]
  21. Kasiviswanathan, R., Longley, M.J., Young, M.J., and Copeland, W.C. (2010) Purification and functional characterization of human mitochondrial DNA polymerase gamma harboring disease mutations. Methods. 51(4):379-384. [Abstract]
  22. Stumpf, J.D., Bailey, C.M., Spell, D., Stillwagon, M., Anderson, K.S., and Copeland, W.C. (2010) mip1 Containing Mutations Associated with MitochondrialDisease Causes Mutagenesis and Depletion of mtDNA in Saccharomyces cerevisiae. Human Molecular Genetics. 19(11):2123-2133. [Abstract]
  23. Prasad, R., Longley, M.J., Sharief, F.S., Hou, E.W., Copeland, W.C., and Wilson, S.H. (2009) Human DNA polymerase theta¸ possesses 5'-dRP lyase activity and functions in single-nucleotide base excision repair in vitro. Nucleic acids research. 37(6):1868-1877. [Abstract]
  24. Kasiviswanathan, R., Longley, M.J., Chan, S.S.L., and Copeland, W.C. (2009) Disease mutations in the human mitochondrial DNA polymerase thumb subdomain impart severe defects in mtDNA replication. J. Biol. Chem. 284(29): 19501-19510. [Abstract]
  25. Chan, S.S.L., and Copeland, W.C. Functional analysis of mutant mitochondrial DNA polymerase involved in disease. In Mitochondrial DNA: Methods and Protocols, 2nd Edition. (J. Stuart, ed) Human Press, July 22, 2009. 554: 59-72. [Abstract]
  26. Longley, M.J., Smith, L.A., and Copeland, W.C. Preparation of human mitochondrial single stranded DNA binding protein. In Mitochondrial DNA: Methods and Protocols, 2nd Edition. (J. Stuart, ed) Humana Press, July 22, 2009. 554: 73-85. [Abstract]
  27. Chan, S.S.L., Naviaux, R.K., Basinger, A.A., Casas, K.A., and Copeland, W.C. (2009) DeNovo Mutation in POLG Leads to Haplotype Insufficiency and Alpers Syndrome. Mitochondrion. (in press) 2009 Jun 6. [Epub ahead of print]. [Abstract]
  28. Prasad, R., Longley, M.J., Sharief, F.S., Hou, E.W., Copeland, W.C., and Wilson, S.H. (2009) Human DNA polymerase theta possesses 5'-dRP lyase activity and functions in single-nucleotide base excision repair in vitro. Nucleic Acids Res. 37(6): 1868-1877. [Abstract]
  29. Stuart, G.R., Humble, M.H., Strand, M.K., and Copeland, W.C. (2009) Transcriptional response to mitochondrial NADH kinase deficiency in saccharomyces cerevisiae. Mitochondrion 9(3):211-221. [Abstract]
  30. Bailey, C.M., Kasiviswanathan, K., Copeland, W.C., and Anderson, K.S. (2009) R964C mutation of DNA polymerase³ imparts increased stavudine toxicity by decreasing nucleoside analog discrimination and impairing polymerase activity. Antimicrobial agents and chemotherapy 53(6):2610-2612. [Abstract]
  31. Chan, S.S.L., and Copeland, W.C. (2009) DNA polymerase gamma and mitochondrial disease: understanding the consequence of POLG mutations. BBA - Bioenergetics 1676(5):312-319. [Abstract]
  32. Stuart, G.R., Copeland, W.C., and Strand, M.K. (2009) Construction and application of a protein and genetic interaction network (Yeast Interactome). Nucleic acids research 37: e54. [Abstract]
  33. Szczesny, B., Tann, A.W., Longley, M.J., Copeland, W.C., and Mitra, S. (2008) Long patch base excision repair in mammalian mitochondrial genomes. The Journal of biological chemistry 283(39):26349-26356. [Abstract]
  34. Wong, L.J., Naviaux, R.K., Brunetti-Pierri, N., Zhang, Q., Schmitt, E.S., Truong, C., Milone, M., Cohen, B.H., Wical, B., Ganesh, J., Basinger, A.A., Burton, B.K., Swoboda, K., Gilbert, D.L., Vanderver, A., Saneto, R.P., Maranda, B., Arnold, G., Abdenur, J.E., Waters, P.J., and Copeland, W.C. (2008) Molecular and clinical genetics of mitochondrial diseases due to POLG mutations. Human mutation 29(9):E150-E172. [Abstract]
  35. Ferraris, S., Clark, S., Garelli, E., Davidzon, G., Moore, S.A., Kardon, R.H., Bienstock, R.J., Longley, M.J., Mancuso, M., Rios, P.G., Hirano, M., Copeland, W.C., and DiMauro, S. (2008) Progressive external ophthalmoplegia, vision, and hearing loss in a patient with mutations in POLG2 and OPA1. Archives of neurology 65(1):125-131. [Abstract]
  36. Copeland, W.C. (2008) Inherited mitochondrial diseases of DNA Replication.Annu. Rev. Med. 59: 131-146. [Abstract]
  37. Copeland, W.C., and Longley, M.J. (2008) DNA2 resolves expanding flap in mitochondrial base excision repair. Mol. Cell. 32, 457-458 [Abstract]
  38. Graziewicz, M.A., Bienstock, R.J., and Copeland, W.C. (2007) 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. Hum. Mol. Genet. 16:2729–2739. [Abstract]
  39. Lewis, W., Day, B.J., Kohler, J.J., Hosseini, S.H., Chan, S.S.L., Green, E., Haase, C.P., Keebaugh, E., Long, R., Ludaway, T., Russ, R., Steltzer, J., Tioleco, N., Santoianni, R., and Copeland, W.C. (2007) Decreased MtDNA, Oxidative Stress, Cardiomyopathy, and Death from Transgenic Cardiac Targeted Human Mutant Polymerase γ. Laboratory Investigation. 87: 326-335. [Abstract]
  40. Chan, S.S.L., Santos, J.H., Meyer, J.N., Mandavilli, B.S., Cook, Jr., D.L., McCash, C.L., Van Houten, B., Copeland, W.C., Walker, V.E., and Bishop, J.B. (2007) Mitochondrial toxicity following perinatal exposure of CD-1 mice to AZT, 3TC, or AZT-3TC. Env. Mol. Mut. 48:190-200. [Abstract]
  41. Chan, S.S.L., Longley, M.J., and Copeland, W.C. (2006) Modulation of the W748S mutation in DNA polymerase γ by the single nucleotide polymorphism, E1143G, in mitochondrial disorders. Hum Mol Genetics 15(23): 3473-3483. [Abstract]
  42. Graziewicz, M.A., Longley, M.J., and Copeland, W.C. (2006) DNA polymerase gamma in mitochondrial DNA replication and repair. Chemical Reviews (Ed. Robert Kuchta) 106(2): 383-405. [Abstract]
  43. Longley, M.J., Clark, S., Yu Wai Man, C., Hudson, G., Durham, S.E., Taylor, R.W., Nightingale, S., Turnbull, D.M., Copeland, W.C., and Chinnery, P.F. (2006) Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia. Am. J. Hum. Genet. 78(6): 1026-1034. [Abstract]
  44. Lewis, W., Kohler, J.J., Hosseini, S.H., Haase, C.P., Copeland. W.C., Bienstock, R.J., Ludaway, T., McNaught, J., Russ, R., Stuart, T., and Santoianni, R. (2006) Antiretroviral nucleosides, deoxynucleotide carrier, and mitochondrial DNA: evidence supporting the DNA pol gamma hypothesis. AIDS, 20(5): 675-684. [Abstract]
  45. Stuart, G.R., Santos, J.H., Strand, M.K., Van Houten, B., and Copeland, W.C. (2006) Mitochondrial and Nuclear DNA Defects in Saccharomyces cerevisiae With Mutations in DNA Polymerase gamma Associated With Progressive External Ophthalmoplegia Hum. Mol. Genetics 15(2): 363-374. [Abstract]
  46. Nguyen, K.V., Sharief, F.S., Chan, S.S.L., Copeland, W.C. and Naviaux, R.K. (2006) Molecular diagnosis of Alpers Syndrome. J. of Hepatology 45(1): 108-116. [Abstract]
  47. Zheng, W., Khrapko, K., Coller, H.A., Thilly, W.G., and Copeland, W.C. (2006) Origins of human mitochondrial point mutations as DNA polymerase gamma–mediated errors. Mutation Research 599(1-2): 11-20. [Abstract]
  48. Chan, S.S.L., Longley, M.J., and Copeland, W.C. (2005) The common A467T mutation in the human mitochondrial DNA polymerase (POLG) compromises catalytic efficiency and interaction with the accessory subunit. J. Biol. Chem. 280(36): 31341-31346. [Abstract]
  49. Chan, S.S.L., Longley, M.J., Naviaux, R.K., and Copeland, W.C. (2005) Mono-allelic POLG expression resulting from nonsense-mediated decay and alternative splicing in a patient with Alpers syndrome. DNA Repair. 4(12): 1381-1389. [Abstract]
  50. Longley, M.J., Graziewicz, M.A., Bienstock, R.J., and Copeland, W.C. (2005) Consequences of mutations in human DNA polymerase gamma. Gene 354: 125-131. [Abstract]
  51. Song, S., Pursell, Z.F., Copeland, W.C., Longley, M.J., Kunkel, T.A., and Mathews, C.K. (2005) DNA precursor asymmetries in mammalian mitochondrial tissues and possible contribution to mitochondrial mutagenesis through reduced replication fidelity. Proc. Natl. Acad. Sci. USA. 102(14): 4990-4995. [Abstract]
  52. Graziewicz, M.A., Longley, M.J., Bienstock, R.J., Zeviani, M., and Copeland W.C. (2004) Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia. Nat. Struct. Mol. Biol. 11(8): 770-776. [Abstract]
  53. Bienstock, R.J., and Copeland, W.C. (2004) Molecular insights into NRTI inhibition and mitochondrial toxicity revealed from a structural model of the human mitochondrial DNA polymerase. Mitochondrion. 4(2-3): 203-213. [Abstract]
  54. Graziewicz, M.A., Sayer, J.M., Jerina, D.J., and Copeland, W.C. (2004) Nucleotide incorporation by human DNA polymerase gamma opposite benzo[a]pyrene and benzo[c]phenanthrene diol epoxide adducts of deoxyguanosine and deoxyadenosine. Nucleic Acids Res. 32(1): 397-405. [Abstract]
  55. Strand, M.K., Stuart, G., Longley, M.J., Graziewicz, M.A., Dominick, O.C., and Copeland, W.C. (2003) POS5 gene of Saccharomyces cerevisiae encodes a mitochondrial NADH kinase required for stability of mitochondrial DNA. Eukaryotic Cell. 2(4): 809-820. [Abstract]
  56. Lim, S.E., Ponamarev, M.V., Longley, M.J., and Copeland, W.C. (2003) Structural determinants in human DNA polymerase gamma account for mitochondrial toxicity from nucleoside analogs J. Mol. Biol. 329(1): 45-57. [Abstract]
  57. Ponamarev, M.V., Longley, M.J., Nguyen, D., Kunkel, T.A., and Copeland, W.C. (2002) Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis. J. Biol. Chem. 277(18): 15225-15228. [Abstract]
  58. Graziewicz, M.A., Day, B.J., and Copeland, W.C. (2002) The mitochondrial DNA polymerase as a target of oxidative damage. Nucleic Acids Res. 30(13): 2817-2824. [Abstract]
  59. Copeland, W.C., Editor (2002) Mitochondrial DNA: Methods and Protocols. Humana Press. Vol. 197. 432 pp. [Abstract]
  60. Longley, M.J., Nguyen, D., Kunkel, T.A., and Copeland, W.C. (2001) The fidelity of human DNA polymerase gamma with and without exonucleolytic proofreading and the p55 accessory subunit. J. Biol. Chem. 276(42): 38555–38562. [Abstract]
  61. Lim, S.E., and Copeland, W.C. (2001) Differential incorporation and removal of antiviral deoxynucleotides by human DNA polymerase gamma. J. Biol. Chem. 276(26): 23616-23623. [Abstract]
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