Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia

Nature Structural and Molecular Biology

Volumn 11, Issue 8, 2004, Pages 770-776

  Graziewicz, Maria A ^a,b   Longley, Matthew J ^a   Bienstock, Rachelle J ^a   Zeviani, Massimo ^c   Copeland, William C ^a  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

^b INSTITUTE OF BIOCHEMISTRY AND BIOPHYSICS   (Poland)

^c DEPARTMENT OF NEUROSURGERY   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

DNA POLYMERASE; MITOCHONDRIAL DNA; NUCLEOTIDE;

AMINO ACID SUBSTITUTION; ARTICLE; AUTOSOMAL DOMINANT DISORDER; CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; DELETION MUTANT; DISEASE SEVERITY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ENZYME ACTIVITY; ENZYME MECHANISM; ENZYME STRUCTURE; GENE; GENE MUTATION; PHENOTYPE; POLG GENE; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN DOMAIN; WILD TYPE;

AMINO ACID MOTIFS; BACTERIAL PROTEINS; CATALYTIC DOMAIN; CRYSTALLOGRAPHY, X-RAY; DNA; DNA-DIRECTED DNA POLYMERASE; GENES, DOMINANT; GLYCINE; HUMANS; KINETICS; MITOCHONDRIA; MODELS, MOLECULAR; MUTAGENESIS, SITE-DIRECTED; MUTATION; NUCLEOTIDES; OPHTHALMOPLEGIA, CHRONIC PROGRESSIVE EXTERNAL; PROTEIN BINDING; PROTEIN FOLDING; RNA-DIRECTED DNA POLYMERASE; STRUCTURE-ACTIVITY RELATIONSHIP; TYROSINE;

EID: 3543039417     PISSN: 15459993     EISSN: None     Source Type: Journal    
DOI: 10.1038/nsmb805     Document Type: Article

References (36)

1. Wallace, D.C. Mitochondrial diseases in man and mouse. Science 283, 1482-1488 (1999).
2. Zeviani, M. et al. An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. Nature 339, 309-311 (1989).
3. Wallace, D.C. Mitochondrial genetics: a paradigm for aging and degenerative diseases? Science 256, 628-632 (1992).
4. Hirano, M. et al. Defects of intergenomic communication: autosomal disorders that cause multiple deletions and depletion of mitochondrial DNA. Semin. Cell. Dev. Biol. 12,417-427(2001).
5. Bohlega, S. et al. Multiple mitochondrial DNA deletions associated with autosomal recessive ophthalmoplegia and severe cardiomyopathy. Neurology 46, 1329-1334 (1996).
6. Suomalainen, A. et al. Autosomal dominant progressive external ophthalmoplegia with multiple deletions of mtDNA: clinical, biochemical, and molecular genetic features of the 10q-linked disease. Neurology 48, 1244-1253 (1997).
7. Kaukonen, J. et al. Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science 289, 782-785 (2000).
8. Spelbrink, J.N. et al. Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. Nat. Genet. 28, 223-231 (2001).
9. Van Goethem, G., Dermaut, B., Lofgren, A., Martin, J.J. & Van Broeckhoven, C. Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat. Genet. 28, 211-212 (2001).
10. Nishino, I., Spinazzola, A. & Hirano, M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283, 689-692 (1999).
11. Ropp, P.A. & Copeland, W.C. Cloning and characterization of the human mitochondrial DNA polymerase, DNA polymerase γ. Genomics 36, 449-458 (1996).
12. Lamantea, E. et al. Mutations of mitochondrial DNA polymerase γ are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. Ann. Neurol. 52, 211-219 (2002).
13. Agostino, A. et al. Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Neurology 60, 1354-1356 (2003).
14. Filosto, M. et al. Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase γ. Arch. Neurol. 60, 1279-1284 (2003).
15. Delarue, M., Poch, O., Tordo, N., Moras, D. & Argos, P. An attempt to unify the structure of polymerases. Protein Eng. 3, 461-467 (1990).
16. Ito, J. & Braithwaite, D.K. Yeast mitochondrial DNA polymerase is related to the family A DNA polymerases. Nucleic Acids Res. 18, 6716 (1990).
17. Ito, J. & Braithwaite, D.K. Compilation and alignment of DNA polymerase sequences. Nucleic Acids Res. 19, 4045-4057 (1991).
18. Ollis, D.L., Brick, P., Hamlin, R., Xuong, N.G. & Steitz, T.A. Structure of large fragment of Escherichia coli DNA polymerase I complexed with dTMP. Nature 313, 762-766 (1985).
19. Kiefer, J.R., Mao, C., Braman, J.C. & Beese, L.S. Visualizing DNA replication in a catalytically active Bacillus DNA polymerase crystal. Nature 391, 304-307 (1998).
20. Doublie, S., Tabor, S., Long, A.M., Richardson, C.C. & Ellenberger, T. Crystal structure of a bacteriophage T7 DNA replication complex at 2.2 Å resolution. Nature 391. 251-258 (1998).
21. Longley, M.J., Ropp, P.A., Lim, S.E. & Copeland, W.C. Characterization of the native and recombinant catalytic subunit of human DNA polymerase γ: identification of residues critical for exonuclease activity and dideoxynucleotide sensitivity. Biochemistry 37, 10529-10539 (1998).
22. Lim, S.E., Longley, M.J. & Copeland, W.C. The mitochondrial p55 accessory subunit of human DNA polymerase γ enhances DNA binding, promotes processive DNA synthesis, and confers N-ethylmaleimide resistance. J. Biol. Chem. 274, 38197-38203 (1999).
23. Longley, M.J., Nguyen, D., Kunkel, T.A. & Copeland, W.C. The fidelity of human DNA polymerase γ with and without exonucleolytic proofreading and the p55 accessory subunit. J. Biol. Chem. 276, 38555-38562 (2001).
24. Lim, S.E., Ponamarev, M.V., Longley, M.J. & Copeland, W.C. Structural determinants in human DNA polymerase γ account for mitochondrial toxicity from nucleoside analogs. J. Mol. Biol. 329, 45-57 (2003).
25. Ponamarev, M.V., Longley, M.J., Nguyen, D., Kunkel, T.A. & Copeland, W.C. Active site mutation in DNA polymerase γ associated with progressive external ophthalmoplegia causes error-prone DNA synthesis. J. Biol. Chem. 277, 15225-15228 (2002).
26. Del Bo, R. et al. Remarkable infidelity of polymerase γA associated with mutations in POLG1 exonuclease domain. Neurology 61, 903-908 (2003).
27. Van Goethem, G. et al. Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul. Disord. 13, 133-142 (2003).
28. Astatke, M., Grindley, N.D. & Joyce, C.M. Deoxynucleoside triphosphate and pyrophosphate binding sites in the catalytically competent ternary complex for the polymerase reaction catalyzed by DNA polymerase I (Klenow fragment). J. Biol. Chem. 270, 1945-1954 (1995).
29. Lim, S.E. & Copeland, W.C. Differential incorporation and removal of antiviral deoxynucleotides by human DNA polymerase γ. J. Biol. Chem. 276, 23616-23623 (2001).
30. Boosalis, M.S., Petruska, J. & Goodman, M.F. DNA polymerase insertion fidelity. Gel assay for site-specific kinetics. J. Biol. Chem. 262, 14689-14696 (1987).
31. Mendelman, L.V., Petruska, J. & Goodman, M.F. Base mispair extension kinetics. Comparison of DNA polymerase α and reverse transcriptase. J. Biol. Chem. 265, 2338-2346(1990).
32. Holm, L. & Sander, C. Protein structure comparison by alignment of distance matrices. J. Mol. Biol. 233, 123-138 (1993).
33. Bienstock, R.J. & Copeland, W.C. Molecular insights into NRTI inhibition and mitochondrial toxicity revealed from a structural model of the human mitochondrial DNA polymerase. Mitochondrion (in the press).
34. Notredame, C., Higgins, D.G. & Heringa, J. T-Coffee: a novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 302, 205-217 (2000).
35. Polesky, A.H., Steitz, T.A., Grindley, N.D. & Joyce, C.M. Identification of residues critical for the polymerase activity of the Klenow fragment of DNA polymerase I from Escherichia coli. J. Biol. Chem. 265, 14579-14591 (1990).
36. Bradford, M.M. A Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254 (1976).