Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling

Human Molecular Genetics

Volumn 18, Issue 2, 2009, Pages 328-340

  Goffart, Steffi ^a   Cooper, Helen M ^a   Tyynismaa, Henna ^b,c   Wanrooij, Sjoerd ^a,d   Suomalainen, Anu ^b,c   Spelbrink, Johannes N ^a  

^a TAMPERE UNIVERSITY HOSPITAL   (Finland)

^b UNIVERSITY OF HELSINKI   (Finland)

^c HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^d UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

HELICASE; MITOCHONDRIAL DNA;

ANIMAL TISSUE; ARTICLE; AUTOSOMAL DOMINANT DISORDER; CELL LINE; CELL PROLIFERATION; CHRONIC PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA; CONTROLLED STUDY; DNA REPLICATION; GENE DELETION; GENE MUTATION; GENETIC PREDISPOSITION; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IMMUNOCYTOCHEMISTRY; MOLECULAR CLONING; MOUSE; NONHUMAN; NORTHERN BLOTTING; PATHOPHYSIOLOGY; PHENOTYPE; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; SOUTHERN BLOTTING; WESTERN BLOTTING; WILD TYPE;

ANIMALS; CELL LINE; DNA HELICASES; DNA REPLICATION; DNA, MITOCHONDRIAL; GENES, DOMINANT; HUMANS; MICE; MICE, TRANSGENIC; MUTATION; OPHTHALMOPLEGIA, CHRONIC PROGRESSIVE EXTERNAL;

MUS;

EID: 58149163606     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddn359     Document Type: Article

References (40)

1. Schaefer, A.M., Blakely, E.L., He, L., Whittaker, R.G., Taylor, R.W., Chinnery, P.F. and Turnbull, D.M. (2008) Prevalence of mitochondrial DNA disease in adults. Ann. Neurol., 63, 35-39.
2. Majamaa, K., Moilanen, J.S., Uimonen, S., Remes, A.M., Salmela, P.I., Karppa, M., Majamaa-Voltti, K.A., Rusanen, H., Sorri, M., Peuhkurinen, K.J. et al. (1998) Epidemiology of A3243G, the mutation for mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes: Prevalence of the mutation in an adult population. Am. J. Hum. Genet., 63, 447-454.
3. Hakonen, A.H., Heiskanen, S., Juvonen, V., Lappalainen, I., Luoma, P.T., Rantamaki, M., Goethem, G.V., Lofgren, A., Hackman, P., Paetau, A. et al. (2005) Mitochondrial DNA polymerase W748S mutation: A common cause of autosomal recessive ataxia with ancient European origin. Am. J. Hum. Genet., 77, 430-441.
4. Winterthun, S., Ferrari, G., He, L., Taylor, R.W., Zeviani, M., Turnbull, D.M., Engelsen, B.A., Moen, G. and Bindoff, L.A. (2005) Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations. Neurology, 64, 1204-1208.
5. Naviaux, R.K. and Nguyen, K.V. (2004) POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann. Neurol., 55, 706-712.
6. Chinnery, P.F. and Zeviani, M. 155th ENMC workshop: Polymerase gamma and disorders of mitochondrial DNA synthesis, 21-23 September 2007, Naarden, The Netherlands. Neuromuscul. Disord., 18, 259-267.
7. Zeviani, M., Servidei, S., Gellera, C., Bertini, E., DiMauro, S. and DiDonato, S. (1989) An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D-loop region. Nature 339, 309-311.
8. Suomalainen, A., Majander, A., Haltia, M., Somer, H., Lonnqvist, J., Savontaus, M.-L. and Peltonen, L. (1992) Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external opthalmoplegia. J. Clin. Invest., 90, 61-66.
9. Suomalainen, A., Majander, A., Wallin, M., Setala, K., Kontula, K., Leinonen, H., Salmi, T., Paetau, A., Haltia, M., Valanne, L. et al. (1997) 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.
10. Yakubovskaya, E., Chen, Z., Carrodeguas, J.A., Kisker, C. and Bogenhagen, D.F. (2006) Functional human mitochondrial DNA polymerase gamma forms a heterotrimer. J. Biol. Chem., 281, 374-382.
11. Yakubovskaya, E., Lukin, M., Chen, Z., Berriman, J., Wall, J.S., Kobayashi, R., Kisker, C. and Bogenhagen, D.F. (2007) The EM structure of human DNA polymerase gamma reveals a localized contact between the catalytic and accessory subunits. Embo J., 26, 4283-4291.
12. Van Goethem, G., Martin, J.J., Dermaut, B., Lofgren, A., Wibail, A., Ververken, D., Tack, P., Dehaene, I., Van Zandijcke, M., Moonen, M. et al. (2003) Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul. Disord., 13, 133-142.
13. Van Goethem, G., Dermaut, B., Lofgren, A., Martin, J.J. and Van Broeckhoven, C. (2001) Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat. Genet., 28, 211-212.
14. Lamantea, E., Tiranti, V., Bordoni, A., Toscano, A., Bono, F., Servidei, S., Papadimitriou, A., Spelbrink, H., Silvestri, L., Casari, G. et al. (2002) Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. Ann. Neurol., 52, 211-219.
15. Agostino, A., Valletta, L., Chinnery, P.F., Ferrari, G., Carrara, F., Taylor, R.W., Schaefer, A.M., Turnbull, D.M., Tiranti, V. and Zeviani, M. (2003) Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Neurology, 60, 1354-1356.
16. 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, 1026-1034.
17. Leipe, D.D., Aravind, L., Grishin, N.V. and Koonin, E.V. (2000) The bacterial replicative helicase DnaB evolved from a RecA duplication. Genome Res., 10, 5-16.
18. Spelbrink, J.N., Li, F.Y., Tiranti, V., Nikali, K., Yuan, Q.P., Tariq, M., Wanrooij, S., Garrido, N., Comi, G., Morandi, L. et al. (2001) 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.
19. Korhonen, J.A., Pham, X.H., Pellegrini, M. and Falkenberg, M. (2004) Reconstitution of a minimal mtDNA replisome in vitro. Embo J., 23, 2423-2429.
20. Tyynismaa, H., Sembongi, H., Bokori-Brown, M., Granycome, C., Ashley, N., Poulton, J., Jalanko, A., Spelbrink, J.N., Holt, I.J. and Suomalainen, A. (2004) Twinkle helicase is essential for mtDNA maintenance and regulates mtDNA copy number. Hum. Mol. Genet., 13, 3219-3227.
21. Matsushima, Y. and Kaguni, L.S. (2007) Differential phenotypes of active site and human autosomal dominant progressive external ophthalmoplegia mutations in Drosophila mitochondrial DNA helicase expressed in Schneider cells. J. Biol. Chem., 282, 9436-9444.
22. Wanrooij, S., Goffart, S., Pohjoismaki, J.L., Yasukawa, T. and Spelbrink, J.N. (2007) Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes. Nucleic Acids Res., 35, 3238-3251.
23. Virgilio, R., Ronchi, D., Hadjigeorgiou, G.M., Bordoni, A., Saladino, F., Moggio, M., Adobbati, L., Kafetsouli, D., Tsironi, E., Previtali, S. et al. (2008) Novel Twinkle (PEO1) gene mutations in mendelian progressive external ophthalmoplegia. J. Neurol., First published on June 30, 2008, 10.1007/s00415-008-0926-3.
24. Hakonen, A.H., Isohanni, P., Paetau, A., Herva, R., Suomalainen, A. and Lonnqvist, T. (2007) Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. Brain, 130, 3032-3040.
25. Sarzi, E., Goffart, S., Serre, V., Chretien, D., Slama, A., Munnich, A., Spelbrink, J.N. and Rotig, A. (2007) Twinkle helicase (PEO1) gene mutation causes mitochondrial DNA depletion. Ann. Neurol., 62 579-587.
26. Tyynismaa, H., Mjosund, K.P., Wanrooij, S., Lappalainen, I., Ylikallio, E., Jalanko, A., Spelbrink, J.N., Paetau, A. and Suomalainen, A. (2005) Mutant mitochondrial helicase Twinkle causes multiple mtDNA deletions and a late-onset mitochondrial disease in mice. Proc. Natl. Acad. Sci. USA, 102, 17687-17692.
27. Garrido, N., Griparic, L., Jokitalo, E., Wartiovaara, J., Van Der Bliek, A.M. and Spelbrink, J.N. (2003) Composition and dynamics of human mitochondrial nucleoids. Mol. Biol. Cell, 14, 1583-1596.
28. Korhonen, J.A., Gaspari, M. and Falkenberg, M. (2003) TWINKLE Has 5′ → 3′ DNA helicase activity and is specifically stimulated by mitochondrial single-stranded DNA-binding protein. J. Biol. Chem., 278, 48627-48632.
29. Korhonen, J.A., Pande, V., Holmlund, T., Farge, G., Pham, X.H., Nilsson, L. and Falkenberg, M. (2008) Structure-function defects of the TWINKLE linker region in progressive external ophthalmoplegia. J. Mol. Biol. 377, 691-705.
30. Farge, G., Holmlund, T., Khvorostova, J., Rofougaran, R., Hofer, A. and Falkenberg, M. (2008) The N-terminal domain of TWINKLE contributes to single-stranded DNA binding and DNA helicase activities. Nucleic Acids Res., 36, 393-403.
31. Guo, S., Tabor, S. and Richardson, C.C. (1999) The linker region between the helicase and primase domains of the bacteriophage T7 gene 4 protein is critical for hexamer formation. J. Biol. Chem., 274, 30303-30309.
32. Donmez, I. and Patel, S.S. (2006) Mechanisms of a ring shaped helicase. Nucleic Acids Res., 34, 4216-4224.
33. Pohjoismaki, J.L., Wanrooij, S., Hyvarinen, A.K., Goffart, S., Holt, I.J., Spelbrink, J.N. and Jacobs, H.T. (2006) Alterations to the expression level of mitochondrial transcription factor A, TFAM, modify the mode of mitochondrial DNA replication in cultured human cells. Nucleic Acids Res., 34, 5815-5828.
34. Krishnan, K.J., Reeve, A.K., Samuels, D.C., Chinnery, P.F., Blackwood, J.K., Taylor, R.W., Wanrooij, S., Spelbrink, J.N., Lightowlers, R.N. and Turnbull, D.M. (2008) What causes mitochondrial DNA deletions in human cells? Nat Genet., 40, 275-279.
35. Spelbrink, J.N., Toivonen, J.M., Hakkaart, G.A., Kurkela, J.M., Cooper, H.M., Lehtinen, S.K., Lecrenier, N., Back, J.W., Speijer, D., Foury, F. et al. (2000) In vivo functional analysis of the human mitochondrial DNA polymerase POLG expressed in cultured human cells. J. Biol. Chem., 275, 24818-24828.
36. Church, G.M. and Gilbert, W. (1984) Genomic sequencing. Proc. Natl. Acad. Sci. USA, 81, 1991-1995.
37. Cooper, H.M. and Spelbrink, J.N. (2008) The human Sirt3 protein deacetylase is exclusively mitochondrial. Biochem J., 411, 279-285.
38. Yasukawa, T., Yang, M.Y., Jacobs, H.T. and Holt, I.J. (2005) A bidirectional origin of replication maps to the major noncoding region of human mitochondrial DNA. Mol. Cell, 18, 651-662.
39. Friedman, K.L. and Brewer, B.J. (1995) Analysis of replication intermediates by two-dimensional agarose gel electrophoresis. Methods Enzymol., 262, 613-627.
40. Brewer, B.J. and Fangman, W.L. (1987) The localization of replication origins on ARS plasmids in S. cerevisiae. Cell, 51, 463-471.