DNA repair deficiency and neurological disease

Nature Reviews Neuroscience

Volumn 10, Issue 2, 2009, Pages 100-112

  McKinnon, Peter J ^a  

^a ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATM PROTEIN; BRCA1 ASSOCIATED RING DOMAIN PROTEIN 1; ENDONUCLEASE; KU ANTIGEN; MITOCHONDRIAL DNA; NIBRIN; POLYDEOXYRIBONUCLEOTIDE SYNTHASE; PROTEIN KINASE; RAD51 PROTEIN; RECQ HELICASE; REPLICATION FACTOR A;

ALZHEIMER DISEASE; ATAXIA TELANGIECTASIA; BLOOM SYNDROME; CELL CYCLE ARREST; CELL METABOLISM; CELL PROLIFERATION; CEREBELLUM ATROPHY; CLINICAL FEATURE; COCKAYNE SYNDROME; COGNITIVE DEFECT; COMPUTER ASSISTED TOMOGRAPHY; DISORDERS OF DNA SYNTHESIS AND REPAIR; DNA DAMAGE; DNA REPAIR; EXCISION REPAIR; FANCONI ANEMIA; GENE MUTATION; GENETIC COMPLEMENTATION; HOMOLOGOUS RECOMBINATION; HUMAN; IONIZING RADIATION; MICROCEPHALY; MITOCHONDRIAL DNA REPLICATION; NERVE CELL DIFFERENTIATION; NEUROLOGIC DISEASE; NUCLEAR MAGNETIC RESONANCE IMAGING; OXIDATIVE STRESS; PARKINSON DISEASE; PERCEPTION DEAFNESS; POINT MUTATION; PRIORITY JOURNAL; REVIEW; ROTHMUND THOMSON SYNDROME; SIGNAL TRANSDUCTION; SPINOCEREBELLAR DEGENERATION; STEM CELL; THYROID HORMONE SYNTHESIS; TRICHOTHIODYSTROPHY; XERODERMA PIGMENTOSUM;

ANIMALS; DNA REPAIR-DEFICIENCY DISORDERS; HUMANS; NERVOUS SYSTEM DISEASES;

EID: 58549092574     PISSN: 1471003X     EISSN: 14710048     Source Type: Journal    
DOI: 10.1038/nrn2559     Document Type: Review

References (201)

1. Bender, A. et al. High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nature Genet. 38, 515-517 (2006).
2. Katyal, S. & McKinnon, P. J. DNA strand breaks, neurodegeneration and aging in the brain. Mech. Ageing Dev. 129, 483-491 (2008).
3. Kraytsberg, Y. et al. Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons. Nature Genet. 38, 518-520 (2006).
4. Nouspikel, T. & Hanawalt, P. C. When parsimony backfires: neglecting DNA repair may doom neurons in Alzheimer's disease. Bioessays 25, 168-173 (2003).
5. Chan, W. Y., Lorke, D. E., Tiu, S. C. & Yew, D. T. Proliferation and apoptosis in the developing human neocortex. Anat. Rec. 267, 261-276 (2002).
6. Dehay, C. & Kennedy, H. Cell-cycle control and cortical development. Nature Rev. Neurosci. 8, 438-450 (2007).
7. Goldowitz, D. & Hamre, K. The cells and molecules that make a cerebellum. Trends Neurosci. 21, 375-382 (1998).
8. Wang, V. Y. & Zoghbi, H. Y. Genetic regulation of cerebellar development. Nature Rev. Neurosci. 2, 484-491 (2001).
9. Zhao, C., Deng, W. & Gage, F. H. Mechanisms and functional implications of adult neurogenesis. Cell 132, 645-660 (2008).
10. Zhang, C. L., Zou, Y., He, W., Gage, F. H. & Evans, R. M. A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451, 1004-1007 (2008).
11. Toni, N. et al. Neurons born in the adult dentate gyrus form functional synapses with target cells. Nature Neurosci. 11, 901-907 (2008).
12. Barnes, D. E., Stamp, G., Rosewell, I., Denzel, A. & Lindahl, T. Targeted disruption of the gene encoding DNA ligase IV leads to lethality in embryonic mice. Curr. Biol. 8, 1395-1398 (1998).
13. Gao, Y. et al. A critical role for DNA end-joining proteins in both lymphogenesis and neurogenesis. Cell 95, 891-902 (1998). References 12 and 13 showed for the first time that repair of DNA DSBs was crucial for the homeostasis of the developing nervous system, thereby linking DNA damage to neurogenesis.
14. Lee, Y. & McKinnon, P. J. Responding to DNA double strand breaks in the nervous system. Neuroscience 145, 1365-1374 (2007).
15. Karanjawala, Z. E., Murphy, N., Hinton, D. R., Hsieh, C. L. & Lieber, M. R. Oxygen metabolism causes chromosome breaks and is associated with the neuronal apoptosis observed in DNA double-strand break repair mutants. Curr. Biol. 12, 397-402 (2002). This paper provided evidence that oxidative stress can lead to increased DNA breaks in the developing nervous system.
16. Saxowsky, T. T. & Doetsch, P. W. RNA polymerase encounters with DNA damage: transcription-coupled repair or transcriptional mutagenesis? Chem. Rev. 106, 474-488 (2006).
17. Zhou, W. & Doetsch, P. W. Effects of abasic sites and DNA single-strand breaks on prokaryotic RNA polymerases. Proc. Natl Acad. Sci. USA 90, 6601-6605 (1993).
18. Brooks, P. J. The 8,5′-cyclopurine-2′-deoxynucleosides: candidate neurodegenerative DNA lesions in xeroderma pigmentosum, and unique probes of transcription and nucleotide excision repair. DNA Repair (Amst.) 7, 1168-1179 (2008).
19. Crowe, S. L., Movsesyan, V. A., Jorgensen, T. J. & Kondratyev, A. Rapid phosphorylation of histone H2A.X following ionotropic glutamate receptor activation. Eur. J. Neurosci. 23, 2351-2361 (2006).
20. Kovtun, I. V. et al. OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature 447, 447-452 (2007).
21. McMurray, C. T. Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease. DNA Repair (Amst.) 7, 1121-1134 (2008).
22. Caldecott, K. W. Single-strand break repair and genetic disease. Nature Rev. Genet. 9, 619-631 (2008).
23. Fousteri, M. & Mullenders, L. H. Transcription-coupled nucleotide excision repair in mammalian cells: molecular mechanisms and biological effects. Cell Res. 18, 73-84 (2008).
24. Kulkarni, A. & Wilson, D. M. The involvement of DNA-damage and -repair defects in neurological dysfunction. Am. J. Hum. Genet. 82, 539-566 (2008).
25. McKinnon, P. J. & Caldecott, K. W. DNA strand break repair and human genetic disease. Annu. Rev. Genomics Hum. Genet. 8, 37-55 (2007).
26. Rass, U., Ahel, I. & West, S. C. Defective DNA repair and neurodegenerative disease. Cell 130, 991-1004 (2007).
27. Subba Rao, K. Mechanisms of disease: DNA repair defects and neurological disease. Nature Clin. Pract. Neurol. 3, 162-172 (2007).
28. Sugasawa, K. Xeroderma pigmentosum genes: functions inside and outside DNA repair. Carcinogenesis 29, 455-465 (2008).
29. Frappart, P. O. & McKinnon, P. J. Ataxia-telangiectasia and related diseases. Neuromolecular Med. 8, 495-511 (2006).
30. McKinnon, P. J. ATM and ataxia telangiectasia. EMBO Rep. 5, 772-776 (2004).
31. Perlman, S., Becker-Catania, S. & Gatti, R. A. Ataxia-telangiectasia: diagnosis and treatment. Semin. Pediatr. Neurol. 10, 173-182 (2003).
32. Taylor, A. M. et al. Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity. Nature 258, 427-429 (1975).
33. Savitsky, K. et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268, 1749-1753 (1995).
34. Shiloh, Y. ATM and related protein kinases: safeguarding genome integrity. Nature Rev. Cancer 3, 155-168 (2003).
35. Shiloh, Y. The ATM-mediated DNA-damage response: taking shape. Trends Biochem. Sci. 31, 402-410 (2006).
36. Helleday, T., Lo, J., van Gent, D. C. & Engelward, B. P. DNA double-strand break repair: from mechanistic understanding to cancer treatment. DNA Repair (Amst.) 6, 923-935 (2007).
37. West, S. C. Molecular views of recombination proteins and their control. Nature Rev. Mol. Cell Biol. 4, 435-445 (2003).
38. Limbo, O. et al. Ctp1 is a cell-cycle-regulated protein that functions with Mre11 complex to control doublestrand break repair by homologous recombination. Mol. Cell 28, 134-146 (2007).
39. Sartori, A. A. et al. Human CtIP promotes DNA end resection. Nature 450, 509-514 (2007).
40. Takeda, S., Nakamura, K., Taniguchi, Y. & Paull, T. T. Ctp1/CtIP and the MRN complex collaborate in the initial steps of homologous recombination. Mol. Cell 28, 351-352 (2007).
41. Wyman, C., Ristic, D. & Kanaar, R. Homologous recombination-mediated double-strand break repair. DNA Repair (Amst.) 3, 827-833 (2004).
42. Lieber, M. R., Ma, Y., Pannicke, U. & Schwarz, K. Mechanism and regulation of human non-homologous DNA end-joining. Nature Rev. Mol. Cell Biol. 4, 712-720 (2003).
43. Bassing, C. H. & Alt, F. W. The cellular response to general and programmed DNA double strand breaks. DNA Repair (Amst.) 3, 781-796 (2004).
44. Lees-Miller, S. P. & Meek, K. Repair of DNA double strand breaks by non-homologous end joining. Biochimie 85, 1161-1173 (2003).
45. Ahnesorg, P., Smith, P. & Jackson, S. P. XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell 124, 301-313 (2006).
46. Buck, D. et al. Cernunnos, a novel nonhomologous end-joining factor, is mutated in human immunodeficiency with microcephaly. Cell 124, 287-299 (2006).
47. O'Driscoll, M. et al. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol. Cell 8, 1175-1185 (2001). This paper and reference 46 report the link between loss of NHEJ function and neuropathology.
48. O'Driscoll, M., Gennery, A. R., Seidel, J., Concannon, P. & Jeggo, P. A. An overview of three new disorders associated with genetic instability: LIG4 syndrome, RS-SCID and ATR-Seckel syndrome. DNA Repair (Amst.) 3, 1227-1235 (2004).
49. Girard, P. M., Kysela, B., Harer, C. J., Doherty, A. J. & Jeggo, P. A. Analysis of DNA ligase IV mutations found in LIG4 syndrome patients: the impact of two linked polymorphisms. Hum. Mol. Genet. 13, 2369-2376 (2004).
50. Celeste, A. et al. Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nature Cell Biol. 5, 675-679 (2003).
51. Sedelnikova, O. A., Pilch, D. R., Redon, C. & Bonner, W. M. Histone H2AX in DNA damage and repair. Cancer Biol. Ther. 2, 233-235 (2003).
52. Ward, I. & Chen, J. Early events in the DNA damage response. Curr. Top. Dev. Biol. 63, 1-35 (2004).
53. Bredemeyer, A. L. et al. ATM stabilizes DNA double-strand-break complexes during V(D)J recombination. Nature 442, 466-470 (2006).
54. Harper, J. W. & Elledge, S. J. The DNA damage response: ten years after. Mol. Cell 28, 739-745 (2007).
55. Kastan, M. B. & Bartek, J. Cell-cycle checkpoints and cancer. Nature 432, 316-323 (2004).
56. Lavin, M. F. & Kozlov, S. ATM activation and DNA damage response. Cell Cycle 6, 931-942 (2007).
57. Wood, J. L. & Chen, J. DNA-damage checkpoints: location, location, location. Trends Cell Biol. 18, 451-455 (2008).
58. Herzog, K. H., Chong, M. J., Kapsetaki, M., Morgan, J. I. & McKinnon, P. J. Requirement for Atm in ionizing radiation-induced cell death in the developing central nervous system. Science 280, 1089-1091 (1998). Together with reference 60, this study showed that ATM function is required for DNA damage-induced apoptosis in immature differentiating neural cells but not in proliferating cells.
59. Jeffers, J. R. et al. Puma is an essential mediator of p53-dependent and -independent apoptotic pathways. Cancer Cell 4, 321-328 (2003).
60. Lee, Y., Chong, M. J. & McKinnon, P. J. Ataxia telangiectasia mutated-dependent apoptosis after genotoxic stress in the developing nervous system is determined by cellular differentiation status. J. Neurosci. 21, 6687-6693 (2001).
61. Takai, H. et al. Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. EMBO J. 21, 5195-5205 (2002).
62. Cimprich, K. A. & Cortez, D. ATR: an essential regulator of genome integrity. Nature Rev. Mol. Cell Biol. 9, 616-627 (2008).
63. Matsuoka, S. et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316, 1160-1166 (2007).
64. Brown, E. J. & Baltimore, D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes Dev. 14, 397-402 (2000).
65. de Klein, A. et al. Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr. Biol. 10, 479-482 (2000).
66. Jazayeri, A. et al. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nature Cell Biol. 8, 37-45 (2006).
67. Burma, S. & Chen, D. J. Role of DNA-PK in the cellular response to DNA double-strand breaks. DNA Repair (Amst.) 3, 909-918 (2004).
68. cs during murine embryogenesis. Curr. Biol. 11, 191-194 (2001).
69. Sedgwick, R. P. & Boder, E. in Handbook of Clinical Neurology (eds Vinken, P., Bruyn, G. & Klawans, H.) 347-423 (Elsevier, New York, 1991).
70. Gatti, R. A. et al. The pathogenesis of ataxia-telangiectasia. Learning from a Rosetta Stone. Clin. Rev. Allergy Immunol. 20, 87-108 (2001).
71. Paula-Barbosa, M. M. et al. Cerebellar cortex ultrastructure in ataxia-telangiectasia. Ann. Neurol. 13, 297-302 (1983).
72. Vinters, H. V., Gatti, R. A. & Rakic, P. in Ataxia-Telangiectasia: Genetics, Neuropathology, and Immunology of a Degenerative Disease of Childhood (eds Gatti, R. A. & Swift, M.) 233-235 (Liss, New York, 1985).
73. Farina, L. et al. Ataxia-telangiectasia: MR and CT findings. J. Comput. Assist. Tomogr. 18, 724-727 (1994).
74. Sardanelli, F. et al. Cranial MRI in ataxia-telangiectasia. Neuroradiology 37, 77-82 (1995).
75. Tavani, F. et al. Ataxia-telangiectasia: the pattern of cerebellar atrophy on MRI. Neuroradiology 45, 315-319 (2003).
76. Barbieri, F. et al. Is the sensory neuropathy in ataxia-telangiectasia distinguishable from that in Friedreich's ataxia? Morphometric and ultrastructural study of the sural nerve in a case of Louis Bar syndrome. Acta Neuropathol. (Berl.) 69, 213-219 (1986).
77. Lelli, S., Trevisan, C. & Negrin, P. Ataxia-telangiectasia: neurophysiological studies in 8 patients. Electromyogr. Clin. Neurophysiol. 35, 311-315 (1995).
78. Carney, J. P. et al. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell 93, 477-486 (1998).
79. Stewart, G. S. et al. The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99, 577-587 (1999). This paper and reference 78 identified mutant MRE11 in people with ATLD, thereby clarifying the link between DNA damage and neurodegeneration.
80. Taylor, A. M., Groom, A. & Byrd, P. J. Ataxia-telangiectasia-like disorder (ATLD)-its clinical presentation and molecular basis. DNA Repair (Amst.) 3, 1219-1225 (2004).
81. Saar, K. et al. The gene for the ataxia-telangiectasia variant, Nijmegen breakage syndrome, maps to a 1-cM interval on chromosome 8q21. Am. J. Hum. Genet. 60, 605-610 (1997).
82. Weemaes, C. M. et al. A new chromosomal instability disorder: the Nijmegen breakage syndrome. Acta Paediatr. Scand. 70, 557-564 (1981).
83. Bekiesinska-Figatowska, M. et al. Cranial MRI in the Nijmegen breakage syndrome. Neuroradiology 42, 43-47 (2000).
84. Digweed, M. & Sperling, K. Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks. DNA Repair (Amst.) 3, 1207-1217 (2004).
85. Bakhshi, S. et al. Medulloblastoma with adverse reaction to radiation therapy in Nijmegen breakage syndrome. J. Pediatr. Hematol. Oncol. 25, 248-251 (2003).
86. Distel, L., Neubauer, S., Varon, R., Holter, W. & Grabenbauer, G. Fatal toxicity following radio- and chemotherapy of medulloblastoma in a child with unrecognized Nijmegen breakage syndrome. Med. Pediatr. Oncol. 41, 44-48 (2003).
87. Maser, R. S., Zinkel, R. & Petrini, J. H. An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele. Nature Genet. 27, 417-421 (2001).
88. Carson, C. T. et al. The Mre11 complex is required for ATM activation and the G2/M checkpoint. EMBO J. 22, 6610-6620 (2003).
89. Uziel, T. et al. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 22, 5612-5621 (2003).
90. Hopfner, K. P. et al. The Rad50 zinc-hook is a structure joining Mre11 complexes in DNA recombination and repair. Nature 418, 562-566 (2002).
91. Moreno-Herrero, F. et al. Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA. Nature 437, 440-443 (2005).
92. Wiltzius, J. J., Hohl, M., Fleming, J. C. & Petrini, J. H. The Rad50 hook domain is a critical determinant of Mre11 complex functions. Nature Struct. Mol. Biol. 12, 403-407 (2005). Together with references 90 and 91, this work provided important details of how MRN functions at a DNA DSB.
93. Falck, J., Coates, J. & Jackson, S. P. Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434, 605-611 (2005).
94. Fernandes, N. et al. DNA damage-induced association of ATM with its target proteins requires a protein interaction domain in the N terminus of ATM. J. Biol. Chem. 280, 15158-15164 (2005).
95. You, Z., Chahwan, C., Bailis, J., Hunter, T. & Russell, P. ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1. Mol. Cell. Biol. 25, 5363-5379 (2005).
96. Kitagawa, R., Bakkenist, C. J., McKinnon, P. J. & Kastan, M. B. Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev. 18, 1423-1438 (2004).
97. Lindahl, T. Instability and decay of the primary structure of DNA. Nature 362, 709-715 (1993).
98. Almeida, K. H. & Sobol, R. W. A unified view of base excision repair: lesion-dependent protein complexes regulated by post-translational modification. DNA Repair (Amst.) 6, 695-711 (2007).
99. David, S. S., O'Shea, V. L. & Kundu, S. Base-excision repair of oxidative DNA damage. Nature 447, 941-950 (2007).
100. Wilson, D. M. & Bohr, V. A. The mechanics of base excision repair, and its relationship to aging and disease. DNA Repair (Amst.) 6, 544-559 (2007).
101. Date, H. et al. Early-onset ataxia with ocular motor apraxia and hypoalbuminemia is caused by mutations in a new HIT superfamily gene. Nature Genet. 29, 184-188 (2001).
102. El-Khamisy, S. F. & Caldecott, K. W. DNA single-strand break repair and spinocerebellar ataxia with axonal neuropathy-1. Neuroscience 145, 1260-1266 (2007).
103. Moreira, M. C. et al. The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin. Nature Genet. 29, 189-193 (2001). Together with reference 101, this study identified the gene that is mutated in AOA1 as aprataxin and implicated a DNA repair deficiency as the potential cause of AOA1.
104. Onodera, O. Spinocerebellar ataxia with ocular motor apraxia and DNA repair. Neuropathology 26, 361-367 (2006).
105. Takashima, H. et al. Mutation of TDP1, encoding a topoisomerase I-dependent DNA damage repair enzyme, in spinocerebellar ataxia with axonal neuropathy. Nature Genet. 32, 267-272 (2002).
106. Aicardi, J. et al. Ataxia-ocular motor apraxia: a syndrome mimicking ataxia-telangiectasia. Ann. Neurol. 24, 497-502 (1988).
107. El-Khamisy, S. F. et al. Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1. Nature 434, 108-113 (2005). This paper provided the important connection between defective DNA SSB repair and neurodegeneration.
108. Le Ber, I. et al. Frequency and phenotypic spectrum of ataxia with oculomotor apraxia 2: a clinical and genetic study in 18 patients. Brain 127, 759-767 (2004).
109. Connelly, J. C. & Leach, D. R. Repair of DNA covalently linked to protein. Mol. Cell 13, 307-316 (2004).
110. Interthal, H. et al. SCAN1 mutant Tdp1 accumulates the enzyme-DNA intermediate and causes camptothecin hypersensitivity. EMBO J. 24, 2224-2233 (2005).
111. Miao, Z. H. et al. Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes. DNA Repair (Amst.) 5, 1489-1494 (2006).
112. Wang, J. C. Cellular roles of DNA topoisomerases: a molecular perspective. Nature Rev. Mol. Cell Biol. 3, 430-440 (2002).
113. Zhou, T. et al. Deficiency in 3′-phosphoglycolate processing in human cells with a hereditary mutation in tyrosyl-DNA phosphodiesterase (TDP1). Nucleic Acids Res. 33, 289-297 (2005).
114. Hirano, R. et al. Spinocerebellar ataxia with axonal neuropathy: consequence of a Tdp1 recessive neomorphic mutation? EMBO J. 26, 4732-4743 (2007).
115. Katyal, S. et al. TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo. EMBO J. 26, 4720-4731 (2007).
116. Ahel, I. et al. The neurodegenerative disease protein aprataxin resolves abortive DNA ligation intermediates. Nature 443, 713-716 (2006). Identified the endogenous DNA lesion that requires aprataxin for its removal.
117. Seidle, H. F., Bieganowski, P. & Brenner, C. Disease-associated mutations inactivate AMP-lysine hydrolase activity of Aprataxin. J. Biol. Chem. 280, 20927-20931 (2005).
118. Rass, U., Ahel, I. & West, S. C. Actions of aprataxin in multiple DNA repair pathways. J. Biol. Chem. 282, 9469-9474 (2007).
119. Sugawara, M. et al. Purkinje cell loss in the cerebellar flocculus in patients with ataxia with ocular motor apraxia type 1/early-onset ataxia with ocular motor apraxia and hypoalbuminemia. Eur. Neurol. 59, 18-23 (2008).
120. Bohr, V. A., Smith, C. A., Okumoto, D. S. & Hanawalt, P. C. DNA repair in an active gene: removal of pyrimidine dimers from the DHFR gene of CHO cells is much more efficient than in the genome overall. Cell 40, 359-369 (1985).
121. Laine, J. P. & Egly, J. M. When transcription and repair meet: a complex system. Trends Genet. 22, 430-436 (2006).
122. Schumacher, B., Garinis, G. A. & Hoeijmakers, J. H. Age to survive: DNA damage and aging. Trends Genet. 24, 77-85 (2008).
123. Min, J. H. & Pavletich, N. P. Recognition of DNA damage by the Rad4 nucleotide excision repair protein. Nature 449, 570-575 (2007).
124. Sugasawa, K. et al. A multistep damage recognition mechanism for global genomic nucleotide excision repair. Genes Dev. 15, 507-521 (2001).
125. Coin, F., Oksenych, V. & Egly, J. M. Distinct roles for the XPB/p52 and XPD/p44 subcomplexes of TFIIH in damaged DNA opening during nucleotide excision repair. Mol. Cell 26, 245-256 (2007).
126. Fan, L. et al. Conserved XPB core structure and motifs for DNA unwinding: implications for pathway selection of transcription or excision repair. Mol. Cell 22, 27-37 (2006).
127. Fan, L. et al. XPD helicase structures and activities: insights into the cancer and aging phenotypes from XPD mutations. Cell 133, 789-800 (2008). This paper, together with references 123-126, provided insights that were crucial for understanding the early events that occur during NER.
128. Liu, H. et al. Structure of the DNA repair helicase XPD. Cell 133, 801-812 (2008).
129. Wolski, S. C. et al. Crystal structure of the FeS cluster-containing nucleotide excision repair helicase XPD. PLoS Biol. 6, e149 (2008).
130. Mu, D., Hsu, D. S. & Sancar, A. Reaction mechanism of human DNA repair excision nuclease. J. Biol. Chem. 271, 8285-8294 (1996).
131. Sijbers, A. M. et al. Xeroderma pigmentosum group F caused by a defect in a structure-specific DNA repair endonuclease. Cell 86, 811-822 (1996).
132. Cleaver, J. E. Cancer in xeroderma pigmentosum and related disorders of DNA repair. Nature Rev. Cancer 5, 564-573 (2005). An important review of the relationship between cancer and neurodegeneration in XP.
133. Nouspikel, T. Nucleotide excision repair and neurological diseases. DNA Repair (Amst.) 7, 1155-1167 (2008).
134. Compe, E. et al. Neurological defects in trichothiodystrophy reveal a coactivator function of TFIIH. Nature Neurosci. 10, 1414-1422 (2007). Showed how deregulated TFIIH can lead to abnormalities in the stabilization of thyroid hormone receptors on DNA-responsive elements in the promoters of their target genes and discussed the implications of this for neuropathology found in TTD.
135. Kraemer, K. H. et al. Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: a complex genotype-phenotype relationship. Neuroscience 145, 1388-1396 (2007).
136. Mimaki, T. et al. Neurological manifestations in xeroderma pigmentosum. Ann. Neurol. 20, 70-75 (1986).
137. Anttinen, A. et al. Neurological symptoms and natural course of xeroderma pigmentosum. Brain 131, 1979-1989 (2008).
138. Robbins, J. H., Kraemer, K. H., Merchant, S. N. & Brumback, R. A. Adult-onset xeroderma pigmentosum neurological disease-observations in an autopsy case. Clin. Neuropathol. 21, 18-23 (2002).
139. Sidwell, R. U. et al. A novel mutation in the XPA gene associated with unusually mild clinical features in a patient who developed a spindle cell melanoma. Br. J. Dermatol. 155, 81-88 (2006).
140. Giannelli, F., Avery, J., Polani, P. E., Terrell, C. & Giammusso, V. Xeroderma pigmentosum and medulloblastoma: chromosomal damage to lymphocytes during radiotherapy. Radiat. Res. 88, 194-208 (1981).
141. Brooks, P. J., Cheng, T. F. & Cooper, L. Do all of the neurologic diseases in patients with DNA repair gene mutations result from the accumulation of DNA damage? DNA Repair (Amst.) 7, 834-848 (2008).
142. Itoh, M. et al. Neurodegeneration in hereditary nucleotide repair disorders. Brain Dev. 21, 326-333 (1999).
143. Henning, K. A. et al. 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 (1995).
144. van der Horst, G. T. et al. Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition. Cell 89, 425-435 (1997).
145. Ito, S. et al. XPG stabilizes TFIIH, allowing transactivation of nuclear receptors: implications for Cockayne syndrome in XP-G/CS patients. Mol. Cell 26, 231-243 (2007).
146. Nouspikel, T. & Hanawalt, P. C. Terminally differentiated human neurons repair transcribed genes but display attenuated global DNA repair and modulation of repair gene expression. Mol. Cell. Biol. 20, 1562-1570 (2000).
147. Kraemer, K. H., Faghri, S., Tamura, D. & Digiovanna, J. J. Trichothiodystrophy: a systematic review of 112 published cases characterizes a wide spectrum of clinical manifestations. J. Med. Genet. 45, 609-621 (2008).
148. Nance, M. A. & Berry, S. A. Cockayne syndrome: review of 140 cases. Am. J. Med. Genet. 42, 68-84 (1992).
149. Friedberg, E. C. & Meira, L. B. Database of mouse strains carrying targeted mutations in genes affecting biological responses to DNA damage Version 7. DNA Repair (Amst.) 5, 189-209 (2006).
150. Sun, X. Z., Harada, Y. N., Takahashi, S., Shiomi, N. & Shiomi, T. Purkinje cell degeneration in mice lacking the xeroderma pigmentosum group G gene. J. Neurosci. Res. 64, 348-354 (2001).
151. Murai, M. et al. Early postnatal ataxia and abnormal cerebellar development in mice lacking Xeroderma pigmentosum Group A and Cockayne syndrome Group B DNA repair genes. Proc. Natl Acad. Sci. USA 98, 13379-13384 (2001).
152. Reid, S. et al. Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer. Nature Genet. 39, 162-164 (2007).
153. Mirchandani, K. D. & D'Andrea, A. D. The Fanconi anemia/BRCA pathway: a coordinator of cross-link repair. Exp. Cell Res. 312, 2647-2653 (2006).
154. D'Andrea, A. D. & Grompe, M. The Fanconi anaemia/BRCA pathway. Nature Rev. Cancer 3, 23-34 (2003).
155. Rahman, N. et al. PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene. Nature Genet. 39, 165-167 (2007).
156. Erkko, H. et al. A recurrent mutation in PALB2 in Finnish cancer families. Nature 446, 316-319 (2007).
157. Offit, K. et al. Shared genetic susceptibility to breast cancer, brain tumors, and Fanconi anemia. J. Natl Cancer Inst. 95, 1548-1551 (2003). Identified medulloblastoma brain tumours as a feature of FA resulting from biallelic BRCA2 mutations.
158. Hunter, N. The RecQ DNA helicases: Jacks-of-all-trades or master-tradesmen? Cell Res. 18, 328-330 (2008).
159. Hickson, I. D. RecQ helicases: caretakers of the genome. Nature Rev. Cancer 3, 169-178 (2003).
160. Harrigan, J. A. & Bohr, V. A. Human diseases deficient in RecQ helicases. Biochimie 85, 1185-1193 (2003).
161. van Brabant, A. J., Stan, R. & Ellis, N. A. DNA helicases, genomic instability, and human genetic disease. Annu. Rev. Genomics Hum. Genet. 1, 409-459 (2000).
162. De Stefano, N. et al. MR evidence of structural and metabolic changes in brains of patients with Werner's syndrome. J. Neurol. 250, 1169-1173 (2003).
163. Kakigi, R., Endo, C., Neshige, R., Kohno, H. & Kuroda, Y. Accelerated aging of the brain in Werner's syndrome. Neurology 42, 922-924 (1992).
164. Postiglione, A. et al. Premature aging in Werner's syndrome spares the central nervous system. Neurobiol. Aging 17, 325-330 (1996).
165. Arning, L. et al. Identification and characterisation of a large Senataxin (SETX) gene duplication in ataxia with ocular apraxia type 2 (AOA2). Neurogenetics 9, 295-299 (2008).
166. Bassuk, A. G. et al. In cis autosomal dominant mutation of Senataxin associated with tremor/ataxia syndrome. Neurogenetics 8, 45-49 (2007).
167. Duquette, A. et al. Mutations in senataxin responsible for Quebec cluster of ataxia with neuropathy. Ann. Neurol. 57, 408-414 (2005).
168. Fogel, B. L. & Perlman, S. Novel mutations in the senataxin DNA/RNA helicase domain in ataxia with oculomotor apraxia 2. Neurology 67, 2083-2084 (2006).
169. Moreira, M. C. et al. Senataxin, the ortholog of a yeast RNA helicase, is mutant in ataxia-ocular apraxia 2. Nature Genet. 36, 225-227 (2004). Identified disruption of a helicase-like factor, senataxin, as the basis for AOA2.
170. Nicolaou, P. et al. A novel c.5308-5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia. BMC Med. Genet. 9, 28 (2008).
171. Chen, Y. Z. et al. Senataxin, the yeast Sen1p orthologue: characterization of a unique protein in which recessive mutations cause ataxia and dominant mutations cause motor neuron disease. Neurobiol. Dis. 23, 97-108 (2006).
172. Suraweera, A. et al. Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage. J. Cell Biol. 177, 969-979 (2007).
173. Nahas, S. A., Duquette, A., Roddier, K., Gatti, R. A. & Brais, B. Ataxia-oculomotor apraxia 2 patients show no increased sensitivity to ionizing radiation. Neuromuscul. Disord. 17, 968-969 (2007).
174. Clements, P. M. et al. The ataxia-oculomotor apraxia 1 gene product has a role distinct from ATM and interacts with the DNA strand break repair proteins XRCC1 and XRCC4. DNA Repair (Amst.) 3, 1493-1502 (2004).
175. Hassin-Baer, S. et al. Absence of mutations in ATM, the gene responsible for ataxia telangiectasia in patients with cerebellar ataxia. J. Neurol. 246, 716-719 (1999).
176. Gueven, N. et al. A subgroup of spinocerebellar ataxias defective in DNA damage responses. Neuroscience 145, 1418-1425 (2007).
177. Frappart, P. O. & McKinnon, P. J. Mouse models of DNA double-strand break repair and neurological disease. DNA Repair (Amst.) 7, 1051-1060 (2008).
178. Frappart, P. O. et al. An essential function for NBS1 in the prevention of ataxia and cerebellar defects. Nature Med. 11, 538-544 (2005).
179. Stucki, M. et al. MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123, 1213-26 (2005).
180. Stucki, M. & Jackson, S. P. γH2AX and MDC1: anchoring the DNA-damage-response machinery to broken chromosomes. DNA Repair (Amst.) 5, 534-543 (2006).
181. Lou, Z. et al. MDC1 maintains genomic stability by participating in the amplification of ATM-dependent DNA damage signals. Mol. Cell 21, 187-200 (2006).
182. Barzilai, A. The contribution of the DNA damage response to neuronal viability. Antioxid. Redox Signal. 9, 211-218 (2007).
183. Ljungman, M. & Lane, D. P. Transcription - guarding the genome by sensing DNA damage. Nature Rev. Cancer 4, 727-737 (2004).
184. Cervos-Navarro, J. & Diemer, N. H. Selective vulnerability in brain hypoxia. Crit. Rev. Neurobiol. 6, 149-182 (1991).
185. Pulsinelli, W. A. Selective neuronal vulnerability: morphological and molecular characteristics. Prog. Brain Res. 63, 29-37 (1985).
186. Chen, P. et al. Oxidative stress is responsible for deficient survival and dendritogenesis in purkinje neurons from ataxia-telangiectasia mutated mutant mice. J. Neurosci. 23, 11453-11460 (2003).
187. DiMauro, S. & Schon, E. A. Mitochondrial disorders in the nervous system. Annu. Rev. Neurosci. 31, 91-123 (2008).
188. Finsterer, J. Central nervous system manifestations of mitochondrial disorders. Acta Neurol. Scand. 114, 217-238 (2006).
189. de Souza-Pinto, N. C., Wilson, D. M., Stevnsner, T. V. & Bohr, V. A. Mitochondrial DNA, base excision repair and neurodegeneration. DNA Repair (Amst.) 7, 1098-1109 (2008).
190. Lakshmipathy, U. & Campbell, C. Mitochondrial DNA ligase III function is independent of Xrcc1. Nucleic Acids Res. 28, 3880-3886 (2000).
191. Weissman, L., de Souza-Pinto, N. C., Stevnsner, T. & Bohr, V. A. DNA repair, mitochondria, and neurodegeneration. Neuroscience 145, 1318-1329 (2007).
192. Druzhyna, N. M., Wilson, G. L. & LeDoux, S. P. Mitochondrial DNA repair in aging and disease. Mech. Ageing Dev. 129, 383-390 (2008).
193. Frappart, P. O., Lee, Y., Lamont, J. & McKinnon, P. J. BRCA2 is required for neurogenesis and suppression of medulloblastoma. EMBO J. 26, 2732-2742 (2007).
194. Nijnik, A. et al. DNA repair is limiting for haematopoietic stem cells during ageing. Nature 447, 686-690 (2007).
195. Rossi, D. J. et al. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447, 725-729 (2007).
196. Ruzankina, Y. et al. Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss. Cell Stem Cell 1, 113-126 (2007). Together with references 194 and 195, this work showed the importance of DNA repair in the maintenance of stem cell populations.
197. Sii-Felice, K. et al. Fanconi DNA repair pathway is required for survival and long-term maintenance of neural progenitors. EMBO J. 27, 770-781 (2008).
198. Yang, J. L., Weissman, L., Bohr, V. A. & Mattson, M. P. Mitochondrial DNA damage and repair in neurodegenerative disorders. DNA Repair (Amst.) 7, 1110-1120 (2008).
199. Kruman, I. I. et al. Cell cycle activation linked to neuronal cell death initiated by DNA damage. Neuron 41, 549-561 (2004).
200. Yang, Y. & Herrup, K. Loss of neuronal cell cycle control in ataxia-telangiectasia: a unified disease mechanism. J. Neurosci. 25, 2522-2529 (2005).
201. Yang, Y. & Herrup, K. Cell division in the CNS: protective response or lethal event in post-mitotic neurons? Biochim. Biophys. Acta 1772, 457-466 (2007).