Mutant huntingtin impairs Ku70-mediated DNA repair

Journal of Cell Biology

Volumn 189, Issue 3, 2010, Pages 425-443

  Enokido, Yasushi ^a   Tamura, Takuya ^a   Ito, Hikaru ^a   Arumughan, Anup ^b   Komuro, Akihiko ^a   Shiwaku, Hiroki ^a   Sone, Masaki ^a   Foulle, Raphaele ^b   Sawada, Hirohide ^c   Ishiguro, Hiroshi ^d   Ono, Tetsuya ^e   Murata, Miho ^f   Kanazawa, Ichiro ^f   Tomilin, Nikolai ^g   Tagawa, Kazuhiko ^a   Wanker, Erich E ^b   Okazawa, Hitoshi ^a,h  

^a TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^b MAX DELBRÜCK CENTER FOR MOLECULAR MEDICINE   (Germany)

^c KOBE TOKIWA UNIVERSITY   (Japan)

^d 1 5 5 Minatojima Minamimachi   (Japan)

^e TOHOKU UNIVERSITY   (Japan)

^f NATIONAL INSTITUTE OF MENTAL HEALTH   (Japan)

^g INSTITUTE OF CYTOLOGY   (Russian Federation)

^h JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

BENZYLOXYCARBONYLLEUCYLLEUCYLLEUCINAL; DNA DEPENDENT PROTEIN KINASE; GENOMIC DNA; HUNTINGTIN; KU ANTIGEN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR; CONTROLLED STUDY; DNA DAMAGE; DNA REPAIR; DOUBLE STRANDED DNA BREAK; FEMALE; GENE EXPRESSION; HISTOPATHOLOGY; HUMAN; HUMAN CELL; HUNTINGTON CHOREA; MALE; MEDIATOR; MOUSE; MUTANT; NERVE CELL; NONHUMAN; NUCLEOTIDE SEQUENCE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION;

ANIMALS; ANTIGENS, NUCLEAR; CELL LINE; DNA BREAKS, DOUBLE-STRANDED; DNA DAMAGE; DNA REPAIR; DNA-BINDING PROTEINS; HELA CELLS; HUMANS; HUNTINGTON DISEASE; MICE; MUTATION; NERVE TISSUE PROTEINS; NEURONS; RATS; RATS, WISTAR;

EID: 77951874547     PISSN: 00219525     EISSN: 00219525     Source Type: Journal    
DOI: 10.1083/jcb.200905138     Document Type: Article

References (107)

1. Arrasate, M., S. Mitra, E.S. Schweitzer, M.R. Segal, and S. Finkbeiner. 2004. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature. 431:805-810. doi:10.1038/nature02998 (Pubitemid 39434070)
2. Bae, B.I., H. Xu, S. Igarashi, M. Fujimuro, N. Agrawal, Y. Taya, S.D. Hayward, T.H. Moran, C. Montell, C.A. Ross, et al. 2005. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron. 47:29-41. doi:10.1016/j.neuron.2005.06.005
3. Bailey, S.M., J. Meyne, D.J. Chen, A. Kurimasa, G.C. Li, B.E. Lehnert, and E.H. Goodwin. 1999. DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes. Proc. Natl. Acad. Sci. USA. 96:14899-14904. doi:10.1073/pnas.96.26.14899
4. Barrios-Rodiles, M., K.R. Brown, B. Ozdamar, R. Bose, Z. Liu, R.S. Donovan, F. Shinjo, Y. Liu, J. Dembowy, I.W. Taylor, et al. 2005. High-throughput mapping of a dynamic signaling network in mammalian cells. Science. 307:1621-1625. doi:10.1126/science.1105776 (Pubitemid 40354744)
5. Bekker-Jensen, S., C. Lukas, R. Kitagawa, F. Melander, M.B. Kastan, J. Bartek, and J. Lukas. 2006. Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. J. Cell Biol. 173:195-206. doi:10.1083/jcb.200510130
6. Bennett, E.J., T.A. Shaler, B. Woodman, K.Y. Ryu, T.S. Zaitseva, C.H. Becker, G.P. Bates, H. Schulman, and R.R. Kopito. 2007. Global changes to the ubiquitin system in Huntington's disease. Nature. 448:704-708. doi:10.1038/nature06022 (Pubitemid 47236860)
7. Bianchi, M.E., and A. Agresti. 2005. HMG proteins: dynamic players in gene regulation and differentiation. Curr. Opin. Genet. Dev. 15:496-506. doi: 10.1016/j.gde.2005.08.007
8. Browne, S.E., R.J. Ferrante, and M.F. Beal. 1999. Oxidative stress in Huntington's disease. Brain Pathol. 9:147-163.
9. Butler, R., and G.P. Bates. 2006. Histone deacetylase inhibitors as therapeutics for polyglutamine disorders. Nat. Rev. Neurosci. 7:784-796. doi:10.1038/nrn1989 (Pubitemid 44435261)
10. Byrum, J., S. Jordan, S.T. Safrany, and W. Rodgers. 2004. Visualization of inositol phosphate-dependent mobility of Ku: depletion of the DNA-PK cofactor InsP6 inhibits Ku mobility. Nucleic Acids Res. 32:2776-2784. doi:10.1093/nar/gkh592 (Pubitemid 38885949)
11. Canman, C.E., D.S. Lim, K.A. Cimprich, Y. Taya, K. Tamai, K. Sakaguchi, E. Appella, M.B. Kastan, and J.D. Siliciano. 1998. Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science. 281:1677-1679. doi:10.1126/science.281.5383.1677
12. Cohen, H.Y., S. Lavu, K.J. Bitterman, B. Hekking, T.A. Imahiyerobo, C. Miller, R. Frye, H. Ploegh, B.M. Kessler, and D.A. Sinclair. 2004. Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis. Mol. Cell. 13:627-638. doi:10.1016/S1097-2765(04)00094-2
13. Cui, L., H. Jeong, F. Borovecki, C.N. Parkhurst, N. Tanese, and D. Krainc. 2006. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell. 127:59-69. doi:10.1016/j.cell.2006.09.015 (Pubitemid 44466642)
14. Dastoor, Z., and J.-L. Dreyer. 2001. Potential role of nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase in apoptosis and oxidative stress. J. Cell Sci. 114:1643-1653. (Pubitemid 32454663)
15. Date, H., O. Onodera, H. Tanaka, K. Iwabuchi, K. Uekawa, S. Igarashi, R. Koike, T. Hiroi, T. Yuasa, Y. Awaya, et al. 2001. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nat. Genet. 29:184-188. doi:10.1038/ng1001-184 (Pubitemid 32952656)
16. de Boer, J., J.O. Andressoo, J. de Wit, J. Huijmans, R.B. Beems, H. van Steeg, G. Weeda, G.T. van der Horst, W. van Leeuwen, A.P. Themmen, et al. 2002. Premature aging in mice deficient in DNA repair and transcription. Science. 296:1276-1279. doi:10.1126/science.1070174 (Pubitemid 34522776)
17. Di Prospero, N.A., and K.H. Fischbeck. 2005. Therapeutics development for triplet repeat expansion diseases. Nat. Rev. Genet. 6:756-765. doi:10.1038/nrg1690
18. Dignam, J.D., R.M. Lebovitz, and R.G. Roeder. 1983. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11:1475-1489. doi:10.1093/nar/11.5.1475
19. El-Khamisy, S.F., G.M. Saifi, M. Weinfeld, F. Johansson, T. Helleday, J.R. Lupski, and K.W. Caldecott. 2005. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. Nature. 434:108-113. doi:10.1038/nature03314
20. Emamian, E.S., M.D. Kaytor, L.A. Duvick, T. Zu, S.K. Tousey, H.Y. Zoghbi, H.B. Clark, and H.T. Orr. 2003. Serine 776 of ataxin-1 is critical for polyglutamine-induced disease in SCA1 transgenic mice. Neuron. 38:375-387. doi:10.1016/S0896-6273(03)00258-7
21. Fairbairn, D.W., P.L. Olive, and K.L. O'Neill. 1995. The comet assay: a comprehensive review. Mutat. Res. 339:37-59.
22. Fernandez-Capetillo, O., A. Lee, M. Nussenzweig, and A. Nussenzweig. 2004. H2AX: the histone guardian of the genome. DNA Repair (Amst.). 3:959-967. doi:10.1016/j.dnarep.2004.03.024
23. Forss-Petter, S., P.E. Danielson, S. Catsicas, E. Battenberg, J. Price, M. Nerenberg, and J.G. Sutcliffe. 1990. Transgenic mice expressing betagalactosidase in mature neurons under neuron-specific enolase promoter control. Neuron. 5:187-197. doi:10.1016/0896-6273(90)90308-3 (Pubitemid 20262697)
24. Gauthier, L.R., B.C. Charrin, M. Borrell-Pagès, J.P. Dompierre, H. Rangone, F.P. Cordelières, J. De Mey, M.E. MacDonald, V. Lessmann, S. Humbert, and F. Saudou. 2004. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell. 118:127-138. doi:10.1016/j.cell.2004.06.018
25. Gil, J.M., and A.C. Rego. 2009. The R6 lines of transgenic mice: a model for screening new therapies for Huntington's disease. Brain Res. Brain Res. Rev. 59:410-431. doi:10.1016/j.brainresrev.2008.12.001
26. Giorgini, F., P. Guidetti, Q. Nguyen, S.C. Bennett, and P.J. Muchowski. 2005. A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nat. Genet. 37:526-531. doi:10.1038/ng1542 (Pubitemid 40617282)
27. Giuliano, P., T. De Cristofaro, A. Affaitati, G.M. Pizzulo, A. Feliciello, C. Criscuolo, G. De Michele, A. Filla, E.V. Avvedimento, and S. Varrone. 2003. DNA damage induced by polyglutamine-expanded proteins. Hum. Mol. Genet. 12:2301-2309. doi:10.1093/hmg/ddg242 (Pubitemid 37160874)
28. Goehler, H., M. Lalowski, U. Stelzl, S. Waelter, M. Stroedicke, U. Worm, A. Droege, K.S. Lindenberg, M. Knoblich, C. Haenig, et al. 2004. A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease. Mol. Cell. 15:853-865. doi:10.1016/j.molcel.2004.09.016 (Pubitemid 39277983)
29. Gu, Y., J. Sekiguchi, Y. Gao, P. Dikkes, K. Frank, D. Ferguson, P. Hasty, J. Chun, and F.W. Alt. 2000. Defective embryonic neurogenesis in Kudeficient but not DNA-dependent protein kinase catalytic subunit-deficient mice. Proc. Natl. Acad. Sci. USA. 97:2668-2673. doi:10.1073/pnas.97.6.2668 (Pubitemid 30159229)
30. Henning, K.A., L. Li, N. Iyer, L.D. McDaniel, M.S. Reagan, R. Legerski, R.A. Schultz, M. Stefanini, A.R. Lehmann, L.V. Mayne, and E.C. Friedberg. 1995. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CSB protein and a subunit of RNA polymerase II TFIIH. Cell. 82:555-564. doi:10.1016/0092-8674(95)90028-4
31. Hoshino, M., M.L. Qi, N. Yoshimura, T. Miyashita, K. Tagawa, Y. Wada, Y. Enokido, S. Marubuchi, P. Harjes, N. Arai, et al. 2006. Transcriptional repression induces a slowly progressive atypical neuronal death associated with changes of YAP isoforms and p73. J. Cell Biol. 172:589-604. doi:10.1083/jcb. 200509132 (Pubitemid 43243879)
32. Hsu, H.L., D. Gilley, E.H. Blackburn, and D.J. Chen. 1999. Ku is associated with the telomere in mammals. Proc. Natl. Acad. Sci. USA. 96:12454-12458. doi:10.1073/pnas.96.22.12454
33. Illuzzi, J., S. Yerkes, H. Parekh-Olmedo, and E.B. Kmiec. 2009. DNA breakage and induction of DNA damage response proteins precede the appearance of visible mutant huntingtin aggregates. J. Neurosci. Res. 87:733-747. doi:10.1002/jnr.21881
34. Inagaki, R., K. Tagawa, M.L. Qi, Y. Enokido, H. Ito, T. Tamura, S. Shimizu, K. Oyanagi, N. Arai, I. Kanazawa, et al. 2008. Omi / HtrA2 is relevant to the selective vulnerability of striatal neurons in Huntington's disease. Eur. J. Neurosci. 28:30-40. doi:10.1111/j.1460-9568.2008.06323.x
35. Ira, G., A. Pellicioli, A. Balijja, X. Wang, S. Fiorani, W. Carotenuto, G. Liberi, D. Bressan, L. Wan, N.M. Hollingsworth, et al. 2004. DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1. Nature. 431:1011-1017. doi:10.1038/nature02964 (Pubitemid 39434425)
36. Ishiguro, H., K. Yamada, H. Sawada, K. Nishii, N. Ichino, M. Sawada, Y. Kurosawa, N. Matsushita, K. Kobayashi, J. Goto, et al. 2001. Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene. J. Neurosci. Res. 65:289-297. doi:10.1002/jnr.1153 (Pubitemid 32727030)
37. Iwata, A., J.C. Christianson, M. Bucci, L.M. Ellerby, N. Nukina, L.S. Forno, and R.R. Kopito. 2005. Increased susceptibility of cytoplasmic over nuclear polyglutamine aggregates to autophagic degradation. Proc. Natl. Acad. Sci. USA. 102:13135-13140. doi:10.1073/pnas.0505801102 (Pubitemid 41324991)
38. Jackson, G.R., I. Salecker, X. Dong, X. Yao, N. Arnheim, P.W. Faber, M.E. MacDonald, and S.L. Zipursky. 1998. Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron. 21:633-642. doi:10.1016/S0896-6273(00)80573-5
39. Jin, S., and D.T. Weaver. 1997. Double-strand break repair by Ku70 requires heterodimerization with Ku80 and DNA binding functions. EMBO J. 16:6874-6885. doi:10.1093/emboj/16.22.6874 (Pubitemid 27503498)
40. Johnston, J.A., C.L. Ward, and R.R. Kopito. 1998. Aggresomes: a cellular response to misfolded proteins. J. Cell Biol. 143:1883-1898. doi:10.1083/jcb.143.7.1883
41. Ju, B.G., V.V. Lunyak, V. Perissi, I. Garcia-Bassets, D.W. Rose, C.K. Glass, and M.G. Rosenfeld. 2006. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science. 312:1798-1802. doi:10.1126/science.1127196
42. Katsuno, M., H. Adachi, M. Doyu, M. Minamiyama, C. Sang, Y. Kobayashi, A. Inukai, and G. Sobue. 2003. Leuprorelin rescues polyglutaminedependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Nat. Med. 9:768-773. doi:10.1038/nm878 (Pubitemid 36749228)
43. Katyal, S., S.F. el-Khamisy, H.R. Russell, Y. Li, L. Ju, K.W. Caldecott, and P.J. McKinnon. 2007. TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo. EMBO J. 26:4720-4731. doi:10.1038/sj.emboj.7601869
44. Klement, I.A., P.J. Skinner, M.D. Kaytor, H. Yi, S.M. Hersch, H.B. Clark, H.Y. Zoghbi, and H.T. Orr. 1998. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell. 95:41-53. doi:10.1016/S0092-8674(00)81781-X
45. Kovtun, I.V., Y. Liu, M. Bjoras, A. Klungland, S.H. Wilson, and C.T. McMurray. 2007. OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature. 447:447-452. doi:10.1038/nature05778
46. Lam, Y.C., A.B. Bowman, P. Jafar-Nejad, J. Lim, R. Richman, J.D. Fryer, E.D. Hyun, L.A. Duvick, H.T. Orr, J. Botas, and H.Y. Zoghbi. 2006. ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology. Cell. 127:1335-1347. doi:10.1016/j.cell.2006.11.038
47. Laroche, T., S.G. Martin, M. Gotta, H.C. Gorham, F.E. Pryde, E.J. Louis, and S.M. Gasser. 1998. Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres. Curr. Biol. 8:653-656. doi:10.1016/S0960-9822(98) 70252-0 (Pubitemid 28257969)
48. Lees-Miller, S.P., K. Sakaguchi, S.J. Ullrich, E. Appella, and C.W. Anderson. 1992. Human DNA-activated protein kinase phosphorylates serines 15 and 37 in the amino-terminal transactivation domain of human p53. Mol. Cell. Biol. 12:5041-5049.
49. Li, H., S.H. Li, H. Johnston, P.F. Shelbourne, and X.J. Li. 2000. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat. Genet. 25:385-389. doi:10.1038/78054
50. Li, L., T.H. Murphy, M.R. Hayden, and L.A. Raymond. 2004. Enhanced striatal NR2B-containing N-methyl-D-aspartate receptor-mediated synaptic currents in a mouse model of Huntington disease. J. Neurophysiol. 92:2738-2746. doi:10.1152/jn.00308.2004 (Pubitemid 40340486)
51. Lieber, M.R., Y. Ma, U. Pannicke, and K. Schwarz. 2003. Mechanism and regulation of human non-homologous DNA end-joining. Nat. Rev. Mol. Cell Biol. 4:712-720. doi:10.1038/nrm1202
52. Lim, J., T. Hao, C. Shaw, A.J. Patel, G. Szabó, J.F. Rual, C.J. Fisk, N. Li, A. Smolyar, D.E. Hill, et al. 2006. A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell. 125:801-814. doi:10.1016/j.cell.2006.03.032 (Pubitemid 43732348)
53. Lim, J., J. Crespo-Barreto, P. Jafar-Nejad, A.B. Bowman, R. Richman, D.E. Hill, H.T. Orr, and H.Y. Zoghbi. 2008. Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1. Nature. 452:713-718. doi:10.1038/nature06731 (Pubitemid 351521076)
54. Lin, M.T., and M.F. Beal. 2006. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature. 443:787-795. doi:10.1038/ nature05292 (Pubitemid 44622683)
55. Lombard, D.B., K.F. Chua, R. Mostoslavsky, S. Franco, M. Gostissa, and F.W. Alt. 2005. DNA repair, genome stability, and aging. Cell. 120:497-512. doi:10.1016/j.cell.2005.01.028 (Pubitemid 40269764)
56. Lu, C., F. Zhu, Y.Y. Cho, F. Tang, T. Zykova, W.Y. Ma, A.M. Bode, and Z. Dong. 2006. Cell apoptosis: requirement of H2AX in DNA ladder formation, but not for the activation of caspase-3. Mol. Cell. 23:121-132. doi:10.1016/j.molcel. 2006.05.023 (Pubitemid 43963445)
57. Mangiarini, L., K. Sathasivam, M. Seller, B. Cozens, A. Harper, C. Hetherington, M. Lawton, Y. Trottier, H. Lehrach, S.W. Davies, and G.P. Bates. 1996. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell. 87:493-506. doi:10.1016/S0092-8674(00)81369-0 (Pubitemid 26374323)
58. Martin, S.G., T. Laroche, N. Suka, M. Grunstein, and S.M. Gasser. 1999. Relocalization of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell. 97:621-633. doi:10.1016/S0092-8674(00)80773-4
59. Metzler, M., V. Legendre-Guillemin, L. Gan, V. Chopra, A. Kwok, P.S. McPherson, and M.R. Hayden. 2001. HIP1 functions in clathrin-mediated endocytosis through binding to clathrin and adaptor protein 2. J. Biol. Chem. 276:39271-39276. doi:10.1074/jbc.C100401200 (Pubitemid 37371302)
60. Murphy, K.P., R.J. Carter, L.A. Lione, L. Mangiarini, A. Mahal, G.P. Bates, S.B. Dunnett, and A.J. Morton. 2000. Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation. J. Neurosci. 20:5115-5123.
61. Okazawa, H. 2003. Polyglutamine diseases: a transcription disorder? Cell. Mol. Life Sci. 60:1427-1439. doi:10.1007/s00018-003-3013-z (Pubitemid 36900524)
62. Okazawa, H., T. Rich, A. Chang, X. Lin, M. Waragai, M. Kajikawa, Y. Enokido, A. Komuro, S. Kato, M. Shibata, et al. 2002. Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death. Neuron. 34:701-713. doi:10.1016/S0896-6273(02)00697-9 (Pubitemid 34628734)
63. Olive, P.L., and J.P. Banáth. 2006. The comet assay: a method to measure DNA damage in individual cells. Nat. Protoc. 1:23-29. doi:10.1038/nprot.2006.5
64. Orii, K.E., Y. Lee, N. Kondo, and P.J. McKinnon. 2006. Selective utilization of nonhomologous end-joining and homologous recombination DNA repair pathways during nervous system development. Proc. Natl. Acad. Sci. USA. 103:10017-10022. doi:10.1073/pnas.0602436103
65. Oshima, J., C.E. Yu, C. Piussan, G. Klein, J. Jabkowski, S. Balci, T. Miki, J. Nakura, T. Ogihara, J. Ells, et al. 1996. Homozygous and compound heterozygous mutations at the Werner syndrome locus. Hum. Mol. Genet. 5:1909-1913. doi:10.1093/hmg/5.12.1909 (Pubitemid 26413633)
66. Pandey, U.B., Z. Nie, Y. Batlevi, B.A. McCray, G.P. Ritson, N.B. Nedelsky, S.L. Schwartz, N.A. DiProspero, M.A. Knight, O. Schuldiner, et al. 2007. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature. 447:859-863. doi:10.1038/ nature05853
67. Panov, A.V., C.A. Gutekunst, B.R. Leavitt, M.R. Hayden, J.R. Burke, W.J. Strittmatter, and J.T. Greenamyre. 2002. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat. Neurosci. 5:731-736.
68. Qi, M.L., K. Tagawa, Y. Enokido, N. Yoshimura, Y. Wada, K. Watase, S. Ishiura, I. Kanazawa, J. Botas, M. Saitoe, et al. 2007. Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases. Nat. Cell Biol. 9:402-414. doi:10.1038/ncb1553
69. Ravikumar, B., C. Vacher, Z. Berger, J.E. Davies, S. Luo, L.G. Oroz, F. Scaravilli, D.F. Easton, R. Duden, C.J. O'Kane, and D.C. Rubinsztein. 2004. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 36:585-595. doi:10.1038/ng1362 (Pubitemid 38715985)
70. Ribes-Zamora, A., I. Mihalek, O. Lichtarge, and A.A. Bertuch. 2007. Distinct faces of the Ku heterodimer mediate DNA repair and telomeric functions. Nat. Struct. Mol. Biol. 14:301-307. doi:10.1038/nsmb1214 (Pubitemid 46608339)
71. Riha, K., J.M. Watson, J. Parkey, and D.E. Shippen. 2002. Telomere length deregulation and enhanced sensitivity to genotoxic stress in Arabidopsis mutants deficient in Ku70. EMBO J. 21:2819-2826. doi:10.1093/emboj/21.11.2819 (Pubitemid 34619397)
72. Ross, C.A., and L.M. Thompson. 2006. Transcription meets metabolism in neurodegeneration. Nat. Med. 12:1239-1241. doi:10.1038/nm1106-1239
73. Roze, E., S. Betuing, C. Deyts, E. Marcon, K. Brami-Cherrier, C. Pagès, S. Humbert, K. Mérienne, and J. Caboche. 2008. Mitogen- and stress-activated protein kinase-1 deficiency is involved in expanded-huntingtin-induced transcriptional dysregulation and striatal death. FASEB J. 22: 1083-1093. doi:10.1096/fj.07-9814 (Pubitemid 351519963)
74. Ruan, Q., M. Lesort, M.E. MacDonald, and G.V. Johnson. 2004. Striatal cells from mutant huntingtin knock-in mice are selectively vulnerable to mitochondrial complex II inhibitor-induced cell death through a non-apoptotic pathway. Hum. Mol. Genet. 13:669-681. doi:10.1093/hmg/ddh082 (Pubitemid 38455955)
75. Sancar, A., L.A. Lindsey-Boltz, K. Unsal-Kaçmaz, and S. Linn. 2004. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73:39-85. doi:10.1146/annurev.biochem.73. 011303.073723 (Pubitemid 39050363)
76. Saudou, F., S. Finkbeiner, D. Devys, and M.E. Greenberg. 1998. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell. 95:55-66. doi:10.1016/S0092-8674(00) 81782-1 (Pubitemid 28458024)
77. Sawa, A., A.A. Khan, L.D. Hester, and S.H. Snyder. 1997. Glyceraldehyde-3-phosphate dehydrogenase: nuclear translocation participates in neuronal and nonneuronal cell death. Proc. Natl. Acad. Sci. USA. 94:11669-11674. doi:10.1073/pnas.94.21.11669 (Pubitemid 27451056)
78. Sawada, H., H. Ishiguro, K. Nishii, K. Yamada, K. Tsuchida, H. Takahashi, J. Goto, I. Kanazawa, and T. Nagatsu. 2007. Characterization of neuronspecific huntingtin aggregates in human huntingtin knock-in mice. Neurosci. Res. 57:559-573. doi:10.1016/j.neures.2007.01.002 (Pubitemid 46412522)
79. Scherzinger, E., R. Lurz, M. Turmaine, L. Mangiarini, B. Hollenbach, R. Hasenbank, G.P. Bates, S.W. Davies, H. Lehrach, and E.E. Wanker. 1997. Huntingtin-encoded polyglutamine expansions form amyloidlike protein aggregates in vitro and in vivo. Cell. 90:549-558. doi:10.1016/S0092-8674(00)80514-0 (Pubitemid 27347244)
80. Schultz, L.B., N.H. Chehab, A. Malikzay, and T.D. Halazonetis. 2000. p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA double-strand breaks. J. Cell Biol. 151:1381-1390. doi:10.1083/jcb.151.7. 1381
81. Shibata, H., D.P. Huynh, and S.M. Pulst. 2000. A novel protein with RNA-binding motifs interacts with ataxin-2. Hum. Mol. Genet. 9:1303-1313. doi:10.1093/hmg/9.9.1303 (Pubitemid 30312479)
82. Siino, J.S., I.B. Nazarov, M.P. Svetlova, L.V. Solovjeva, R.H. Adamson, I.A. Zalenskaya, P.M. Yau, E.M. Bradbury, and N.V. Tomilin. 2002. Photobleaching of GFP-labeled H2AX in chromatin: H2AX has low diffusional mobility in the nucleus. Biochem. Biophys. Res. Commun. 297:1318-1323. doi:10.1016/S0006- 291X(02)02383-5
83. Singaraja, R.R., S. Hadano, M. Metzler, S. Givan, C.L. Wellington, S. Warby, A. Yanai, C.A. Gutekunst, B.R. Leavitt, H. Yi, et al. 2002. HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis. Hum. Mol. Genet. 11:2815-2828. doi:10.1093/hmg/11. 23.2815
84. Sittler, A., R. Lurz, G. Lueder, J. Priller, H. Lehrach, M.K. Hayer-Hartl, F.U. Hartl, and E.E. Wanker. 2001. Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease. Hum. Mol. Genet. 10:1307-1315. doi:10.1093/hmg/10.12.1307 (Pubitemid 32600484)
85. Soong, B.W., and H.L. Paulson. 2007. Spinocerebellar ataxias: an update. Curr. Opin. Neurol. 20:438-446. doi:10.1097/WCO.0b013e3281fbd3dd
86. Sordet, O., C.E. Redon, J. Guirouilh-Barbat, S. Smith, S. Solier, C. Douarre, C. Conti, A.J. Nakamura, B.B. Das, E. Nicolas, et al. 2009. Ataxia telangiectasia mutated activation by transcription- and topoisomerase I-induced DNA double-strand breaks. EMBO Rep. 10:887-893. doi:10.1038/embor.2009.97
87. St-Pierre, J., S. Drori, M. Uldry, J.M. Silvaggi, J. Rhee, S. Jäger, C. Handschin, K. Zheng, J. Lin, W. Yang, et al. 2006. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell. 127:397-408. doi:10.1016/j.cell.2006.09.024 (Pubitemid 44572377)
88. Steffan, J.S., A. Kazantsev, O. Spasic-Boskovic, M. Greenwald, Y.Z. Zhu, H. Gohler, E.E. Wanker, G.P. Bates, D.E. Housman, and L.M. Thompson. 2000. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA. 97:6763-6768. doi:10.1073/pnas.100110097 (Pubitemid 30412788)
89. Stiff, T., M. O'Driscoll, N. Rief, K. Iwabuchi, M. Löbrich, and P.A. Jeggo. 2004. ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 64:2390-2396. doi:10.1158/0008-5472. CAN-03-3207 (Pubitemid 38523891)
90. Sugars, K.L., and D.C. Rubinsztein. 2003. Transcriptional abnormalities in Huntington disease. Trends Genet. 19:233-238. doi:10.1016/S0168-9525(03) 00074-X
91. Suraweera, A., O.J. Becherel, P. Chen, N. Rundle, R. Woods, J. Nakamura, M. Gatei, C. Criscuolo, A. Filla, L. Chessa, et al. 2007. Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage. J. Cell Biol. 177:969-979. doi:10.1083/jcb.200701042 (Pubitemid 46955702)
92. Tagawa, K., M. Hoshino, T. Okuda, H. Ueda, H. Hayashi, S. Engemann, H. Okado, M. Ichikawa, E.E. Wanker, and H. Okazawa. 2004. Distinct aggregation and cell death patterns among different types of primary neurons induced by mutant huntingtin protein. J. Neurochem. 89:974-987. doi:10.1111/j.1471-4159.2004. 02372.x (Pubitemid 38684744)
93. Tagawa, K., S. Marubuchi, M.L. Qi, Y. Enokido, T. Tamura, R. Inagaki, M. Murata, I. Kanazawa, E.E. Wanker, and H. Okazawa. 2007. The induction levels of heat shock protein 70 differentiate the vulnerabilities to mutant huntingtin among neuronal subtypes. J. Neurosci. 27:868-880. doi:10.1523/JNEUROSCI.4522-06. 2007 (Pubitemid 46174507)
94. Takashima, H., C.F. Boerkoel, J. John, G.M. Saifi, M.A. Salih, D. Armstrong, Y. Mao, F.A. Quiocho, B.B. Roa, M. Nakagawa, et al. 2002. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nat. Genet. 32:267-272. doi:10.1038/ng987
95. The Huntington's Disease Collaborative Research Group. 1993. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell. 72:971-983. doi:10.1016/0092-8674(93)90585-E
96. Thomas, J.O., and A.A. Travers. 2001. HMG1 and 2, and related 'architectural' DNA-binding proteins. Trends Biochem. Sci. 26:167-174. doi:10.1016/S0968-0004(01)01801-1
97. Tibbetts, R.S., K.M. Brumbaugh, J.M. Williams, J.N. Sarkaria, W.A. Cliby, S.Y. Shieh, Y. Taya, C. Prives, and R.T. Abraham. 1999. A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev. 13:152-157. doi:10.1101/gad.13.2.152 (Pubitemid 29061945)
98. Tomimatsu, N., C.G. Tahimic, A. Otsuki, S. Burma, A. Fukuhara, K. Sato, G. Shiota, M. Oshimura, D.J. Chen, and A. Kurimasa. 2007. Ku70/80 modulates ATM and ATR signaling pathways in response to DNA double strand breaks. J. Biol. Chem. 282:10138-10145. doi:10.1074/jbc.M611880200 (Pubitemid 47093392)
99. Travers, A.A. 2003. Priming the nucleosome: a role for HMGB proteins? EMBO Rep. 4:131-136. doi:10.1038/sj.embor.embor741
100. Troelstra, C., A. van Gool, J. de Wit, W. Vermeulen, D. Bootsma, and J.H. Hoeijmakers. 1992. ERCC6, a member of a subfamily of putative helicases, is involved in Cockayne's syndrome and preferential repair of active genes. Cell. 71:939-953. doi:10.1016/0092-8674(92)90390-X
101. Venkatraman, P., R. Wetzel, M. Tanaka, N. Nukina, and A.L. Goldberg. 2004. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol. Cell. 14:95-104. doi:10.1016/S1097-2765(04)00151-0 (Pubitemid 38469912)
102. Wang, J.C. 2002. Cellular roles of DNA topoisomerases: a molecular perspective. Nat. Rev. Mol. Cell Biol. 3:430-440. doi:10.1038/nrm831 (Pubitemid 34685700)
103. Waragai, M., E. Junn, M. Kajikawa, S. Takeuchi, I. Kanazawa, M. Shibata, M.M. Mouradian, and H. Okazawa. 2000. PQBP-1/Npw38, a nuclear protein binding to the polyglutamine tract, interacts with U5-15kD/dim1p via the carboxyl-terminal domain. Biochem. Biophys. Res. Commun. 273:592-595. doi:10.1006/bbrc.2000.2992 (Pubitemid 30599030)
104. Weydt, P., V.V. Pineda, A.E. Torrence, R.T. Libby, T.F. Satterfield, E.R. Lazarowski, M.L. Gilbert, G.J. Morton, T.K. Bammler, A.D. Strand, et al. 2006. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab. 4:349-362. doi:10.1016/j.cmet.2006.10.004 (Pubitemid 44645069)
105. Wyttenbach, A., O. Sauvageot, J. Carmichael, C. Diaz-Latoud, A.P. Arrigo, and D.C. Rubinsztein. 2002. Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum. Mol. Genet. 11:1137-1151. doi:10.1093/hmg/11.9.1137 (Pubitemid 34521094)
106. Yu, C.E., J. Oshima, Y.H. Fu, E.M. Wijsman, F. Hisama, R. Alisch, S. Matthews, J. Nakura, T. Miki, S. Ouais, et al. 1996. Positional cloning of the Werner's syndrome gene. Science. 272:258-262. doi:10.1126/science.272.5259.258 (Pubitemid 26119137)
107. Zhang, P., C. Dilley, and M.P. Mattson. 2007. DNA damage responses in neural cells: Focus on the telomere. Neuroscience. 145:1439-1448. doi:10.1016/j.neuroscience.2006.11.052 (Pubitemid 46602741)