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DNA Repair and Neurological Diseases

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Cell Death and Diseases of the Nervous System

Abstract

The central nervous system (CNS) is composed of a heterogeneous population of cells with differing replicative and transcriptional programs. Current approaches to the analysis of DNA repair are beginning to address differences in repair pathways that correlate with patterns of gene expression and DNA replication. Early studies of DNA repair in the nervous system largely ignored the inherent heterogeneity in repair, allowing the assumption that repair in the bulk genome was representative of the total genome including active genes. In few organs was this more misleading than in the brain, where neurons can transcribe up to 30% of the expressed genome. Animal studies indicated continued accumulation of DNA damage in neurons and a reduction in repair capacity with advancing age. On the other hand, it was generally believed that the brain was relatively resistant to DNA damage.

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References

  1. Ames BN, Shigenaga MK, Hagen TM Oxidants, antioxidants and degenerative diseases of aging. Proc Natl Acad Sci USA 1994, 90: 7915–7922.

    Article  Google Scholar 

  2. Dizdaroglu M. Characterization of free radical induced DNA damage to DNA by the combined use of enzymatic hydrolysis and gas chromatography-mass spectrometry. J Chromatogr 1986, 367: 357–366.

    Article  PubMed  CAS  Google Scholar 

  3. Friedberg EC, Walker GC, Siede W. DNA Repair and Mutagenesis. ASM Press, Washington, D.C., 1995.

    Google Scholar 

  4. Modrich P, Lahue, R. Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Ann Rev Biochem 1996, 65: 101–133.

    Article  PubMed  CAS  Google Scholar 

  5. Goodrich JA, Tijan R. Transcription factors TFIIE and TFIIH and ATP hydrolysis direct promoter clearance by RNA polymerase II. Cell 1994, 77: 145–156.

    Article  PubMed  CAS  Google Scholar 

  6. Wood R. DNA repair in eukaryotes. Ann Rev Biochem 1996, 65: 135–138.

    Article  PubMed  CAS  Google Scholar 

  7. Friedberg EC. Relationship between DNA repair and transcription. Ann Rev Biochem 1996, 65: 14–43.

    Article  Google Scholar 

  8. Bohr VA, Smith CA, Okumoto DS, Hanawalt PC. 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 1985, 40: 359–369.

    Article  PubMed  CAS  Google Scholar 

  9. Bohr VA. The fine structure of DNA repair and genomic instability. Carcinogenesis 1995, 16: 2885–2895.

    Article  PubMed  CAS  Google Scholar 

  10. Tornaletti S, Pfeifer G. Slow repair of pyrimidine dimers at p53 mutational hot spots in skin cancer. Science 1994, 263: 1436–1438.

    Article  PubMed  CAS  Google Scholar 

  11. Sancar A. Nucleotide excision repair. Ann Rev Bioch 1994, 65: 43–81.

    Article  Google Scholar 

  12. Kirchgessner C, Brown JM. Radiosensitivity, DNA double strand break repair and VDJ recombination, in DNA Repair Mechanisms: Impact on Human Disease and Cancer (Vos JH, ed.), RG Landes, Austin, TX, 1995, pp. 349–373.

    Google Scholar 

  13. Lavin MF, Khana K, Beamish H, Spring K, Watters D, Shiloh D. Relationship of the ataxia-telangiectasia protein ATM to phosphoinositide 3-kinase. TIBS 1995, 20: 382–383.

    PubMed  CAS  Google Scholar 

  14. Korr H, Schultze B. Unscheduled DNA synthesis in various types of cells of the mouse brain in vivo. Exp Brian Res 1989, 74: 573–578.

    CAS  Google Scholar 

  15. Desousa J, De Boni U, Cinader B. Age-related decrease in ultraviolet induced DNA repair in neurons but not in lymph node cells of inbred mice. Mech. Aging Dev 1986, 36: 1–12.

    Article  CAS  Google Scholar 

  16. Heytig C, van’t Veer, L. Repair of ethylnitrosourea-induced DNA damage in the newborn rat. II. Localization of unscheduled DNA synthesis in the developing rat brain. Carcinogenesis 1981, 2: 1173–1180.

    Article  Google Scholar 

  17. Jensen L, Linn S. A reduced rate of bulky DNA adduct removal is coincident with differentiation of human neuroblastoma cells induced by nerve growth factor. Mol Cell Biol 1988, 8: 3964–3968.

    PubMed  CAS  Google Scholar 

  18. Kuenzle, CC. Enzymology of DNA replication and repair in the brain. Brain Res Rev 1985, 10: 231–245.

    Article  CAS  Google Scholar 

  19. Rao S. Genomic damage and its repair in the young and aging brain. Mol Neurobiol 1993, 7: 23–48.

    Article  PubMed  CAS  Google Scholar 

  20. Todo T, Ryo H, Yamamoto K, Toh H, Inui T, Ayaki H, Nomura T, Ikenaga M. Similarity among the Drosophila (6-4) photolyase, a human photolyase homologue, and the DNA photolyase-blue-light photoreceptor family. Science 1996, 272: 109–112.

    Article  PubMed  CAS  Google Scholar 

  21. Goto K, Numata M, Komura J, Ono Bestor T, Kondo H. Expression of DNA methyltransferase gene in mature and immature neurons as well as proliferating cells in mice. Differentiation 1994, 56: 39–44.

    PubMed  CAS  Google Scholar 

  22. Krokan H, Haugen A, Myrnes B, Guddal P Repair of premutagenic DNA lesions in human fetal tissues: evidence for low levels of O6-methylguanine-DNA methyltransferase and uracil-DNA glycosylase activity in some tissues. Carcinogenesis 1983, 4: 1559–1564.

    Article  PubMed  CAS  Google Scholar 

  23. Bilen J, Itel ME, Niedergang C, Okazaki H, Mandel P. Poly(adenosine diphosphate ribose) polymerase activity in neuronal and glial nuclei from bovine cerebrum. Neurochemical Res 1981, 6: 1253–1263.

    Article  CAS  Google Scholar 

  24. Ivanov VA, Tretyak TM, Afonin YN. Excision of apurinic and/or apyrimidinic sites from DNA by nucleolytical enzymes from rat brain. Eur J Biochem 1988, 172: 155–159.

    Article  PubMed  CAS  Google Scholar 

  25. Dragunow M. Ref-1 expression in adult mammalian neurons and astrocytes. Neurose Lett 1995, 191: 189–192.

    Article  CAS  Google Scholar 

  26. Nakaya N, Sawasaki Y, Teraoka H, Nakajima, H, Tsukda K. Changes of DNA ligase in the developing rat brain. J Biochem 1977, 81: 1575–1577.

    PubMed  CAS  Google Scholar 

  27. Inoue N, Kato T. Nuclear DNA ligase and its action on chromatin DNA in neuronal, glial, and liver nuclei isolated from adult guinea pigs. J Neurochem 1980, 34: 1574–1583.

    Article  PubMed  CAS  Google Scholar 

  28. Me Whir J, Selfridge J, Harrison DJ, Squires S, Melton DW. Mice with DNA repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning. Nature Genetics 1993, 5: 217–224.

    Article  Google Scholar 

  29. Dabholkar MD, Berger MS, Vionnet JA, Egwuagu C, Silber JR, Yu JJ, Reed E. Malignant and nonmalignant brain tissues differ in their messenger RNA expression patterns for ERCC1 and ERCC2. Cancer Res 1995, 55: 1261–1266.

    PubMed  CAS  Google Scholar 

  30. Hubank M, Mayne L. Expression of the excision repair gene, ERCC3 (excision repair cross-complementing), during mouse development. Dev. Brain Res 1994, 81: 66–76.

    Article  CAS  Google Scholar 

  31. Mounkes LC, Jones RS, Liang B, Gelbart W, Fuller MT. A drosophila model for Xeroderma Pigmentosum and Cockaynes syndrome: haywire encodes the fly homologue of ERCC3, a human excision repair gene. Cell 1992, 71: 925–937.

    Article  PubMed  CAS  Google Scholar 

  32. Zhou Z, Walter C. Expression of the DNA repair gene XRCC1 in baboon tissues. Mut Res 1995, 348: 111–116.

    Article  CAS  Google Scholar 

  33. Brooks PJ, Marietta C, Goldman D. DNA mismatch repair and methylation in adult brain neurons. J Neurosci 1996, 16: 939–945.

    PubMed  CAS  Google Scholar 

  34. Hanawalt PC, Gee P, Ho L, Hsu RK, Kane CJM. Genomic heterogeneity of DNA repair. Ann NY Acad Sci 1992, 633: 17–25.

    Article  Google Scholar 

  35. Cleaver JC, Kraemer K. Xeroderma Pigmentosum in (Scriver CR, Beaudet AL, Sly WS, Valle D, eds.) Metabolic and Molecular Basis of Inherited Disease. McGraw Hill, New York, 1995, pp. 4393–4419.

    Google Scholar 

  36. Kraemer KH, Lee MM, Scotto J. Xeroderma Pigmentosum, cutaneous, ocular and Neurologic abnormalities in 830 published cases. Arch Derm 1987, 123: 241–249.

    Article  PubMed  CAS  Google Scholar 

  37. Robbins JH, et al. Neurologic disease in Xeroderma Pigmentosum. Brain 1991, 14: 1335–1361.

    Article  Google Scholar 

  38. Hoeijmakers JHJ. Nucleotide excision repair: Molecular and clinical implications, in DNA Repair Mechanisms: Impact on Human Disease and Cancer (Vos, J.H., ed.), RG Landes, Austin TX, 1995, pp. 125–150.

    Google Scholar 

  39. Evans MK, Robbins JH, Ganges MB, Tarone RE, Nairn RS, and Bohr VA. Gene-specific DNA repair in xeroderma pigmentosum complementation groups A, C, D, and F. Relation to cellular survival and clinical features. J Biol Chem 1993, 268: 4839–4847.

    PubMed  CAS  Google Scholar 

  40. Venema J, Mullenders LHF, Natarajan AT, Van Zeeland AA, Mayne LV. The genetic defect in Cockayne syndrome is associated with a defect in repair of UV-induced DNA damage in transcriptionally active DNA. Proc Natl Acad Sci USA 1990, 87: 4707–4711.

    Article  PubMed  CAS  Google Scholar 

  41. Andrews AD, Barrett SF, Robbins, JH. Xeroderma Pigmentosum neurological abnormalities correlate with colony-forming ability after ultraviolet radiation. Proc Natl Acad Sci USA 1978, 75: 1984–1988.

    Article  PubMed  CAS  Google Scholar 

  42. Moriwaki S, Nishigori C, Imamura S, Takahashi C, Fujimoto N, Takebe H. A case of xeroderma pigmentosum complementation group F with neurological abnormalities. Br J Derm 1993, 128: 91–94.

    Article  CAS  Google Scholar 

  43. Robbins JH, Brumback RA, Moshell AN. Clinically asymptomatic xeroderma pigmentosum neurological disease in an adult: evidence for a neurodegeneration in later life caused by defective DNA repair. Eur Neurol 1993, 33: 188–90.

    Article  PubMed  CAS  Google Scholar 

  44. Cockayne EA. Dwarfism with retinal atrophy and deafness. Arch Dis Child 1936, 11: 1–8.

    Article  PubMed  CAS  Google Scholar 

  45. Henning KA, Li L, Iyer N, McDaniel LD, Reagan MS, Legerski R, Schultz RA, Stefanini M, Lehmann AR, Mayne LV, Friedberg EC. The Cockayne syndrome group A gene encodes a WD repeat protein that interacts with CS-B protein and a subunit of RNA polymerase II TFIIH. Cell 1995, 82: 555–564.

    Article  PubMed  CAS  Google Scholar 

  46. Nance MA, Berry SA. Cockayne syndrome: Review of 140 cases. Am J Med Genet 1992, 42: 68–84.

    Article  PubMed  CAS  Google Scholar 

  47. Lehmann AR. Cockaynes syndrome and trichothiodystrophy: Defective repair without cancer. Cancer Rev 1987, 7: 82–103.

    Google Scholar 

  48. Soffer D, Grotsky HW, Rapin I, Suzuki K. Cockayne syndrome: Unusual neuropathological findings and review of the literature. Ann Neurol 1979, 6: 340–348.

    Article  PubMed  CAS  Google Scholar 

  49. Balajee AS, Ma A, Dianov GL, Friedberg EC, Bohr VA. Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome cells. Proc Nat Acad Sci USA 1997, 94: 4306–4311.

    Article  PubMed  CAS  Google Scholar 

  50. Dianov GL, Houle JF, Iyer N, Bohr VA, Friedberg EC. Reduced RNA Polymerase II Transcription in Extracts of Cockayne Syndrome and Xeroderma Pigmentosum/Cockayne Syndrome Cells. Nucleic Acids Res 1997, (in press).

    Google Scholar 

  51. Itin PH, Pittelkow MR. Trichothiodystrophy: Review of sulfiir-deficient brittle hair syndromes and association with the ectodermal dysplasias. J Am Acad Derm 1990, 22: 705–717.

    Article  PubMed  CAS  Google Scholar 

  52. Coulter DL, Beals TF, Allen RJ. Neurotrichosis: Hair-shaft abnormalities associated with neurological diseases. Dev Med Child Neurol 1982, 5: 634–44.

    Google Scholar 

  53. Chen E, Cleaver JE, Weber CA, Packman S, Barkovich AJ, Koch TK, Williams ML, Golabi M, Price VH. Trichothiodystrophy: Clinical spectrum, central nervous system imaging, and biochemical characterization of two siblings. J Invest Dermatol 1994, 103: 154S-158S.

    Google Scholar 

  54. Takayama K, Salazar EP, Broughton BC, Lehmann AR, Sarasin A, Thompson LH, Weber CA. Defects in the DNA repair and transcription gene ERCC2 (XPD) in trichothiodystrophy. Am J Hum Genet. 1996, 58: 263–270.

    PubMed  CAS  Google Scholar 

  55. Vermeulen W, et al. (1994) Three unusual repair deficiencies associated with transcription factor BTF2(TFIIH): evidence for the existence of a transcription syndrome, in Cold Spring Harbor Symposia on Quantitative Biology, LIX, 1994, 317–329.

    Google Scholar 

  56. Swift M, Reitnauer PJ, Morrell D, Chase CL. Breast and other cancers in families with Ataxia-Telangiectasia. N Engl J Med 1987, 316: 1289–94.

    Article  PubMed  CAS  Google Scholar 

  57. Swift M, Morrell D, Massey RB, Chase CL. Incidence of cancer in 161 families affected by Ataxia-Telangiectasia. N Engl J Med 1991, 325: 1831–1836.

    Article  PubMed  CAS  Google Scholar 

  58. Sedgwick RP. Neurological abnormalities in ataxia-telangiectasia in Ataxia-Telangiectasia—A Cellular and Molecular Link Between Cancer, Neuropathology, and Immune Deficiency (Bridges BA, Harnden DG, eds.), Wiley, NY, 1982, pp. 23–35.

    Google Scholar 

  59. Vinters HV, Gatti RA, Rakic P. Sequence of cellular events in cerebellar ontogeny relevant to expression of neuronal abnormalities in ataxia-telangiectasia, inAtaxia-Telangiectasia: Genetics, Neuropathology, and Immunology of a Degenerative Disease of Childhood (Gatti, RA, Swift M, eds.) Alan R. Liss, NY, 1985, pp. 233–255.

    Google Scholar 

  60. Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, Ersoy F, Foroud T, Jaspers NG, Lange K, et al. Localization of an ataxia-telangiectasia gene to chromosome 111q22-23. Nature 1988, 336: 577–580.

    Article  PubMed  CAS  Google Scholar 

  61. Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 1995, 268: 1749–1753.

    Article  PubMed  CAS  Google Scholar 

  62. Hartley KO, Gell, D, Smith GC, Zhang H, Divecha N, Connelly MA, Admon A, Lees-Miller SP, Anderson CW, Jackson SP. DNA-dependent protein kinase catalytic subunit: A relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell 1995, 82: 849–856.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Brian G. Fuller
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  2. Vilhelm Bohr
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Editors and Affiliations

  1. The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Vassilis E. Koliatsos MD

  2. Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA

    Rajiv R. Ratan MD, PhD

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Fuller, B.G., Bohr, V. (1999). DNA Repair and Neurological Diseases. In: Koliatsos, V.E., Ratan, R.R. (eds) Cell Death and Diseases of the Nervous System. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4612-1602-5_12

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  • DOI: https://doi.org/10.1007/978-1-4612-1602-5_12

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4612-7213-7

  • Online ISBN: 978-1-4612-1602-5

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