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Genome Integrity pp 363–380Cite as

Genomic Instability in Fanconi Anaemia and Nijmegen Breakage Syndrome

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Part of the book series: Genome Dynamics and Stability ((GENOME,volume 1))

Abstract

An increased mutation rate in somatic cells is often manifested as spontaneous chromosomal instability. Patients suffering from the so-called chromosome instability syndromes have a greatly increased cancer risk as a major symptom. The complexity of the involvement of the underlying genes in the cellular response to DNA damage is well illustrated by the disorders Nijmegen Breakage Syndrome (NBS) and Fanconi anaemia (FA). These two Mendelian diseases show increased spontaneous chromosomal damage and hypersensitivity towards two of the most destructive environmental carcinogens–ionising radiation in the case of Nijmegen Breakage Syndrome and bifunctional alkylating agents in Fanconi anaemia. This review examines the similarities and differences between these two disorders of DNA repair.

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References

  1. Akkari YM, Bateman RL, Reifsteck CA, D'Andrea AD, Olson SB, Grompe M (2001) The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase. Mol Genet Metab 74:403–412

    Article  PubMed  CAS  Google Scholar 

  2. Anderson DE, Trujillo KM, Sung P, Erickson HP (2001) Structure of the Rad50 Mre11 DNA repair complex from Saccharomyces cerevisiae by electron microscopy. J Biol Chem 276:37027–37033

    Article  PubMed  CAS  Google Scholar 

  3. Antoccia A, Stumm M, Saar K, Ricordy R, Maraschio P, Tanzarella C (1999) Impaired p53-mediated DNA damage response, cell-cycle disturbance and chromosome aberrations in Nijmegen breakage syndrome lymphoblastoid cell lines. Int J Radiat Biol 75:583–591

    Article  PubMed  CAS  Google Scholar 

  4. Arwert F, Rooimans MA, Westerveld A, Simons JW, Zdzienicka MZ (1991) The Chinese hamster cell mutant V-H4 is homologous to Fanconi anemia (complementation group A). Cytogenet Cell Genet 56:23–26

    Article  PubMed  CAS  Google Scholar 

  5. Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506

    Article  PubMed  CAS  Google Scholar 

  6. Bressan DA, Baxter BK, Petrini JH (1999) The Mre11-Rad50-Xrs2 protein complex facilitates homologous recombination-based double-strand break repair in Saccharomyces cerevisiae. Mol Cell Biol 19:7681–7687

    PubMed  CAS  Google Scholar 

  7. Bridge WL, Vandenberg CJ, Franklin RJ, Hiom K (2005) The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair. Nat Genet 37:953–957

    Article  PubMed  CAS  Google Scholar 

  8. Buscemi G et al. (2001) Chk2 activation dependence on Nbs1 after DNA damage. Mol Cell Biol 21:5214–5222

    Article  PubMed  CAS  Google Scholar 

  9. Carney JP et al. (1998) 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

    Article  PubMed  CAS  Google Scholar 

  10. Chen HT et al. (2000) Response to RAG-mediated VDJ cleavage by NBS1 and gamma-H2AX. Science 290:1962–1965

    Article  PubMed  CAS  Google Scholar 

  11. Chen PL, Chen CF, Chen Y, Xiao J, Sharp ZD, Lee WH (1998) The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment. Proc Natl Acad Sci USA 95:5287–5292

    Article  PubMed  CAS  Google Scholar 

  12. Clatworthy AE, Valencia-Burton MA, Haber JE, Oettinger MA (2005) The MRE11-RAD50-XRS2 complex, in addition to other non-homologous end-joining factors, is required for V(D)J joining in yeast. J Biol Chem 280:20247–20252

    Article  PubMed  CAS  Google Scholar 

  13. Cressman VL, Backlund DC, Avrutskaya AV, Leadon SA, Godfrey V, Koller BH (1999) Growth retardation, DNA repair defects, and lack of spermatogenesis in BRCA1-deficient mice. Mol Cell Biol 19:7061–7075

    PubMed  CAS  Google Scholar 

  14. de Jager M, van Noort J, van Gent DC, Dekker C, Kanaar R, Wyman C (2001) Human Rad50/Mre11 is a flexible complex that can tether DNA ends. Mol Cell 8:1129–1135

    Article  PubMed  Google Scholar 

  15. Deans B, Griffin CS, Maconochie M, Thacker J (2000) Xrcc2 is required for genetic stability, embryonic neurogenesis and viability in mice. Embo J 19:6675–6685

    Article  PubMed  CAS  Google Scholar 

  16. Demuth I et al. (2004) An inducible null mutant murine model of Nijmegen breakage syndrome proves the essential function of NBS1 in chromosomal stability and cell viability. Hum Mol Genet 13:2385–2397

    Article  PubMed  CAS  Google Scholar 

  17. Deng CX, Wang RH (2003) Roles of BRCA1 in DNA damage repair: a link between development and cancer. Hum Mol Genet 12 Spec No 1:R113–123

    Article  CAS  Google Scholar 

  18. Digweed M et al. (2002) Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia. Carcinogenesis 23:1121–1126

    Article  PubMed  CAS  Google Scholar 

  19. Donoho G et al. (2003) Deletion of Brca2 exon 27 causes hypersensitivity to DNA crosslinks, chromosomal instability, and reduced life span in mice. Genes Chromosomes Cancer 36:317–331

    Article  PubMed  CAS  Google Scholar 

  20. Dronkert ML, Kanaar R (2001) Repair of DNA interstrand cross-links. Mutat Res 486:217–247

    PubMed  CAS  Google Scholar 

  21. Dumon-Jones V et al. (2003) Nbn heterozygosity renders mice susceptible to tumor formation and ionizing radiation-induced tumorigenesis. Cancer Res 63:7263–7269

    PubMed  CAS  Google Scholar 

  22. Folias A et al. (2002) BRCA1 interacts directly with the Fanconi anemia protein FANCA. Hum Mol Genet 11:2591–2597

    Article  PubMed  CAS  Google Scholar 

  23. Frappart PO et al. (2005) An essential function for NBS1 in the prevention of ataxia and cerebellar defects. Nat Med 11:538–544

    Article  PubMed  CAS  Google Scholar 

  24. Freie BW et al. (2004) A role for the Fanconi anemia C protein in maintaining the DNA damage-induced G2 checkpoint. J Biol Chem 279:50986–50993

    Article  PubMed  CAS  Google Scholar 

  25. Garcia-Higuera I et al. (2001) Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Mol Cell 7:249–262

    Article  PubMed  CAS  Google Scholar 

  26. Gatei M et al. (2000) ATM-dependent phosphorylation of nibrin in response to radiation exposure. Nat Genet 25:115–119

    Article  PubMed  CAS  Google Scholar 

  27. Gennery AR et al. (2004) The clinical and biological overlap between Nijmegen Breakage Syndrome and Fanconi anemia. Clin Immunol 113:214–219

    Article  PubMed  CAS  Google Scholar 

  28. Girard PM, Riballo E, Begg AC, Waugh A, Jeggo PA (2002) Nbs1 promotes ATM dependent phosphorylation events including those required for G1/S arrest. Oncogene 21:4191–4199

    Article  PubMed  CAS  Google Scholar 

  29. Godthelp BC, Artwert F, Joenje H, Zdzienicka MZ (2002) Impaired DNA damage-induced nuclear Rad51 foci formation uniquely characterizes Fanconi anemia group D1. Oncogene 21:5002–5005

    Article  PubMed  CAS  Google Scholar 

  30. Hopfner KP, Karcher A, Craig L, Woo TT, Carney JP, Tainer JA (2001) Structural biochemistry and interaction architecture of the DNA double-strand break repair Mre11 nuclease and Rad50-ATPase. Cell 105:473–485

    Article  PubMed  CAS  Google Scholar 

  31. Howlett NG et al. (2002) Biallelic inactivation of BRCA2 in Fanconi anemia. Science 297:606–609

    Article  PubMed  CAS  Google Scholar 

  32. Hussain S et al. (2004) Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways. Hum Mol Genet 13:1241–1248

    Article  PubMed  CAS  Google Scholar 

  33. Hussain S, Witt E, Huber PA, Medhurst AL, Ashworth A, Mathew CG (2003) Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1. Hum Mol Genet 12:2503–2510

    Article  PubMed  CAS  Google Scholar 

  34. Ito A et al. (1999) Expression of full-length NBS1 protein restores normal radiation responses in cells from Nijmegen breakage syndrome patients. Biochem Biophys Res Commun 265:716–721

    Article  PubMed  CAS  Google Scholar 

  35. Ivanov EL, Sugawara N, Fishman-Lobell J, Haber JE (1996) Genetic requirements for the single-strand annealing pathway of double-strand break repair in Saccharomyces cerevisiae. Genetics 142:693–704

    CAS  Google Scholar 

  36. Joenje H et al. (1997) Evidence for at least eight Fanconi anemia genes. Am J Hum Genet 61:940–944

    Article  PubMed  CAS  Google Scholar 

  37. Johnson RD, Liu N, Jasin M (1999) Mammalian XRCC2 promotes the repair of DNA double-strand breaks by homologous recombination. Nature 401:397–399

    PubMed  CAS  Google Scholar 

  38. Jongmans W, Vuillaume M, Chrzanowska K, Smeets D, Sperling K, Hall J (1997) Nijmegen breakage syndrome cells fail to induce the p53-mediated DNA damage response following exposure to ionizing radiation. Mol Cell Biol 17:5016–5022

    PubMed  CAS  Google Scholar 

  39. Kitagawa R, Bakkenist CJ, McKinnon PJ, Kastan MB (2004) Phosphorylation of SMC1 is a critical downstream event in the ATM-NBS1-BRCA1 pathway. Genes Dev 18:1423–1438

    Article  PubMed  CAS  Google Scholar 

  40. Kracker S et al. (2005) Nibrin functions in Ig class-switch recombination. Proc Natl Acad Sci USA 102:1584–1589

    Article  PubMed  CAS  Google Scholar 

  41. Lahdesmaki A, Taylor AM, Chrzanowska KH, Pan-Hammarstrom Q (2004) Delineation of the role of the Mre11 complex in class switch recombination. J Biol Chem 279:16479–16487

    Article  PubMed  CAS  Google Scholar 

  42. Lankenau D-H, Gloor GB (1998) In vivo gap repair in Drosophila: a one-way street with many destinations. Bioessays 20:317–327

    Article  PubMed  CAS  Google Scholar 

  43. Larminat F, Germanier M, Papouli E, Defais M (2004) Impairment of homologous recombination control in a Fanconi anemia-like Chinese hamster cell mutant. Biol Cell 96:545–552

    Article  PubMed  CAS  Google Scholar 

  44. Lee JH, Paull TT (2004) Direct activation of the ATM protein kinase by the Mre11/Rad50/ Nbs1 complex. Science 304:93–96

    Article  PubMed  CAS  Google Scholar 

  45. Lee JH, Paull TT (2005) ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308:551–554

    Article  PubMed  CAS  Google Scholar 

  46. Levitus M et al. (2004) Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes. Blood 103:2498–2503

    Article  PubMed  CAS  Google Scholar 

  47. Levitus M et al. (2005) The DNA helicase BRIP1 is defective in Fanconi anemia complementation group. J Nat Genet 37:934–935

    Article  CAS  Google Scholar 

  48. Levran O et al. (2005) The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia. Nat Genet 37:931–933

    Article  PubMed  CAS  Google Scholar 

  49. Lewis LK, Karthikeyan G, Westmoreland JW, Resnick MA (2002) Differential suppression of DNA repair deficiencies of Yeast rad50, mre11 and xrs2 mutants by EXO1 and TLC1 (the RNA component of telomerase). Genetics 160:49–62

    CAS  Google Scholar 

  50. Lobachev K, Vitriol E, Stemple J, Resnick MA, Bloom K (2004) Chromosome fragmentation after induction of a double-strand break is an active process prevented by the RMX repair complex. Curr Biol 14:2107–2112

    Article  PubMed  CAS  Google Scholar 

  51. Ma JL, Kim EM, Haber JE, Lee SE (2003) Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. Mol Cell Biol 23:8820–8828

    Article  PubMed  CAS  Google Scholar 

  52. Manolis KG, Nimmo ER, Hartsuiker E, Carr AM, Jeggo PA, Allshire RC (2001) Novel functional requirements for non-homologous DNA end joining in Schizosaccharomyces pombe. Embo J 20:210–221

    Article  PubMed  CAS  Google Scholar 

  53. Maser RS, Zinkel R, Petrini JH (2001) An alternative mode of translation permits production of a variant NBS1 protein from the common Nijmegen breakage syndrome allele. Nat Genet 27:417–421

    Article  PubMed  CAS  Google Scholar 

  54. Meetei AR et al. (2003) A novel ubiquitin ligase is deficient in Fanconi anemia. Nat Genet 35:165–170

    Article  PubMed  CAS  Google Scholar 

  55. Meetei AR et al. (2005) A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet 37:958–963

    Article  PubMed  CAS  Google Scholar 

  56. Moore JK, Haber JE (1996) Cell cycle and genetic requirements of two pathways of nonhomologous end-joining repair of double-strand breaks in Saccharomyces cerevisiae. Mol Cell Biol 16:2164–2173

    PubMed  CAS  Google Scholar 

  57. Moreau S, Ferguson JR, Symington LS (1999) The nuclease activity of Mre11 is required for meiosis but not for mating type switching, end joining, or telomere maintenance. Mol Cell Biol 19:556–566

    PubMed  CAS  Google Scholar 

  58. Moynahan ME, Cui TY, Jasin M (2001a) Homology-directed dna repair, mitomycin-c resistance, and chromosome stability is restored with correction of a Brca1 mutation. Cancer Res 61:4842–4850

    Google Scholar 

  59. Moynahan ME, Pierce AJ, Jasin M (2001b) BRCA2 is required for homology-directed repair of chromosomal breaks. Mol Cell 7:263–272

    Google Scholar 

  60. Nakanishi K et al. (2002) Interaction of FANCD2 and NBS1 in the DNA damage response. Nat Cell Biol 4:913–920

    Article  PubMed  CAS  Google Scholar 

  61. Nakanishi K et al. (2005) Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. Proc Natl Acad Sci USA 102:1110–1115

    Article  PubMed  CAS  Google Scholar 

  62. Nelms BE, Maser RS, MacKay JF, Lagally MG, Petrini JH (1998) In situ visualization of DNA double-strand break repair in human fibroblasts. Science 280:590–592

    Article  PubMed  CAS  Google Scholar 

  63. New HV et al. (2005) Nijmegen breakage syndrome diagnosed as Fanconi anaemia. Pediatr Blood Cancer 44:494–499

    Article  PubMed  Google Scholar 

  64. Niedzwiedz W, Mosedale G, Johnson M, Ong CY, Pace P, Patel KJ (2004) The Fanconi anaemia gene FANCC promotes homologous recombination and error-prone DNA repair. Mol Cell 15:607–620

    Article  PubMed  CAS  Google Scholar 

  65. Pan Q, Petit-Frere C, Lahdesmaki A, Gregorek H, Chrzanowska KH, Hammarstrom L (2002) Alternative end joining during switch recombination in patients with ataxia-telangiectasia. Eur J Immunol 32:1300–1308

    Article  PubMed  CAS  Google Scholar 

  66. Paull TT, Gellert M (1999) Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex. Genes Dev 13:1276–1288

    Article  PubMed  CAS  Google Scholar 

  67. Petersen S et al. (2001) AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching. Nature 414:660–665

    Article  PubMed  CAS  Google Scholar 

  68. Petrini JH, Donovan JW, Dimare C, Weaver DT (1994) Normal V(D)J coding junction formation in DNA ligase I deficiency syndromes. J Immunol 152:176–183

    PubMed  CAS  Google Scholar 

  69. Pichierri P, Averbeck D, Rosselli F (2002) DNA cross-link-dependent RAD50/MRE11/NBS1 subnuclear assembly requires the Fanconi anemia C protein. Hum Mol Genet 11:2531–2546

    Article  PubMed  CAS  Google Scholar 

  70. Pichierri P, Rosselli F (2004) The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways. Embo J 23:1178–1187

    Article  PubMed  CAS  Google Scholar 

  71. Richardson C, Elliott B, Jasin M (1999) Chromosomal double-strand breaks introduced in mammalian cells by expression of I-Sce I endonuclease. Methods Mol Biol 113:453–463

    PubMed  CAS  Google Scholar 

  72. Rothfuss A, Grompe M (2004) Repair kinetics of genomic interstrand DNA cross-links: evidence for DNA double-strand break-dependent activation of the Fanconi anemia/BRCA pathway. Mol Cell Biol 24:123–134

    Article  PubMed  CAS  Google Scholar 

  73. Saar K et al. (1997) 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

    PubMed  CAS  Google Scholar 

  74. Schroeder TM, German J (1974) Bloom's syndrome and Fanconi's anemia: demonstration of two distinctive patterns of chromosome disruption and rearrangement. Humangenetik 25:299–306

    Article  PubMed  CAS  Google Scholar 

  75. Seemanova E (1990) An increased risk for malignant neoplasms in heterozygotes for a syndrome of microcephaly, normal intelligence, growth retardation, remarkable facies, immunodeficiency and chromosomal instability. Mutat Res 238:321–324

    PubMed  CAS  Google Scholar 

  76. Seyschab H et al. (1995) Comparative evaluation of diepoxybutane sensitivity and cell cycle blockage in the diagnosis of Fanconi anemia. Blood 85:2233–2237

    PubMed  CAS  Google Scholar 

  77. Shima H, Suzuki M, Shinohara M (2005) Isolation and characterization of novel xrs2 mutations in Saccharomyces cerevisiae. Genetics 170:71–85

    Article  CAS  Google Scholar 

  78. Smith S, Gupta A, Kolodner RD, Myung K (2005) Suppression of gross chromosomal rearrangements by the multiple functions of the Mre11-Rad50-Xrs2 complex in Saccharomyces cerevisiae. DNA Repair (Amst) 4:606–617

    Article  CAS  Google Scholar 

  79. Stark JM, Pierce AJ, Oh J, Pastink A, Jasin M (2004) Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Mol Cell Biol 24:9305–9316

    Article  PubMed  CAS  Google Scholar 

  80. Steffen J et al. (2004) Increased cancer risk of heterozygotes with NBS1 germline mutations in Poland. Int J Cancer 111:67–71

    Article  PubMed  CAS  Google Scholar 

  81. Stiff T, Reis C, Alderton GK, Woodbine L, O'Driscoll M, Jeggo PA (2005) Nbs1 is required for ATR-dependent phosphorylation events. Embo J 24:199–208

    Article  PubMed  CAS  Google Scholar 

  82. Strathdee CA, Gavish H, Shannon WR, Buchwald M (1992) Cloning of cDNAs for Fanconi's anaemia by functional complementation. Nature 358:434

    PubMed  CAS  Google Scholar 

  83. Sullivan KE, Veksler E, Lederman H, Lees-Miller SP (1997) Cell cycle checkpoints and DNA repair in Nijmegen breakage syndrome. Clin Immunol Immunopathol 82:43–48

    CAS  Google Scholar 

  84. Taniguchi T, Garcia-Higuera I, Andreassen PR, Gregory RC, Grompe M, D'Andrea AD (2002) S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51. Blood 100:2414–2420

    Article  PubMed  CAS  Google Scholar 

  85. Tauchi H et al. (2002) Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells. Nature 420:93–98

    Article  PubMed  CAS  Google Scholar 

  86. The Fanconi anaemia/breast cancer consortium (1996) Positional cloning of the Fanconi anaemia group A gene. Nat Genet 14:324–328

    Google Scholar 

  87. Timmers C et al. (2001) Positional cloning of a novel Fanconi anemia gene, FANCD2. Mol Cell 7:241–248

    Article  PubMed  CAS  Google Scholar 

  88. Tsuzuki T et al. (1996) Targeted disruption of the Rad51 gene leads to lethality in embryonic mice. Proc Natl Acad Sci USA 93:6236–6240

    Article  PubMed  CAS  Google Scholar 

  89. Tutt A et al. (2001) Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences. Embo J 20:4704–4716

    Article  PubMed  CAS  Google Scholar 

  90. Uziel T, Lerenthal Y, Moyal L, Andegeko Y, Mittelman L, Shiloh Y (2003) Requirement of the MRN complex for ATM activation by DNA damage. Embo J 22:5612–5621

    Article  PubMed  CAS  Google Scholar 

  91. van Engelen BG, Hiel JA, Gabreels FJ, van den Heuvel LP, van Gent DC, Weemaes CM (2001) Decreased immunoglobulin class switching in Nijmegen Breakage syndrome due to the DNA repair defect. Hum Immunol 62:1324–1327

    Article  PubMed  Google Scholar 

  92. Varon R et al. (1998) Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell 93:467–476

    Article  PubMed  CAS  Google Scholar 

  93. Wang X, Andreassen PR, D'Andrea AD (2004) Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Mol Cell Biol 24:5850–5862

    Article  PubMed  CAS  Google Scholar 

  94. Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (2000) BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures. Genes Dev 14:927–939

    PubMed  CAS  Google Scholar 

  95. Weksberg R, Buchwald M, Sargent P, Thompson MW, Siminovitch L (1979) Specific cellular defects in patients with Fanconi anemia. J Cell Physiol 101:311–323

    Article  PubMed  CAS  Google Scholar 

  96. Xu B, Kim S, Kastan MB (2001) Involvement of Brca1 in S-phase and G(2)-phase checkpoints after ionizing irradiation. Mol Cell Biol 21:3445–3450

    Article  PubMed  CAS  Google Scholar 

  97. Yabuki M, Fujii MM, Maizels N (2005) The MRE11-RAD50-NBS1 complex accelerates somatic hypermutation and gene conversion of immunoglobulin variable regions. Nat Immunol 6:730–736

    Article  PubMed  CAS  Google Scholar 

  98. Yamaguchi-Iwai Y et al. (1999) Mre11 is essential for the maintenance of chromosomal DNA in vertebrate cells. Embo J 18:6619–6629

    Article  PubMed  CAS  Google Scholar 

  99. Yamamoto K et al. (2003) Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells. Mol Cell Biol 23:5421–5430

    Article  PubMed  CAS  Google Scholar 

  100. Yamazaki V, Wegner RD, Kirchgessner CU (1998) Characterization of cell cycle checkpoint responses after ionizing radiation in Nijmegen breakage syndrome cells. Cancer Res 58:2316–2322

    PubMed  CAS  Google Scholar 

  101. Yang YG et al. (2005) The Fanconi anemia group A protein modulates homologous repair of DNA double-strand breaks in mammalian cells. Carcinogenesis 26:1731–1740

    Article  PubMed  CAS  Google Scholar 

  102. Yeo TC et al. (2000) V(D)J rearrangement in Nijmegen breakage syndrome. Mol Immunol 37:1131–1139

    Article  PubMed  CAS  Google Scholar 

  103. You Z, Chahwan C, Bailis J, Hunter T, Russell P (2005) ATM Activation and Its Recruitment to Damaged DNA Require Binding to the C Terminus of Nbs1. Mol Cell Biol 25:5363–5379

    Article  PubMed  CAS  Google Scholar 

  104. Yuan SS, Chang HL, Lee EY (2003) Ionizing radiation-induced Rad51 nuclear focus formation is cell cycle-regulated and defective in both ATM(-/-) and c-Abl(-/-) cells. Mutat Res 525:85–92

    PubMed  CAS  Google Scholar 

  105. Zhu J, Petersen S, Tessarollo L, Nussenzweig A (2001) Targeted disruption of the Nijmegen breakage syndrome gene NBS1 leads to early embryonic lethality in mice. Curr Biol 11:105–109

    Article  PubMed  CAS  Google Scholar 

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  1. Institut für Humangenetik, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Martin Digweed

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Digweed, M. (2006). Genomic Instability in Fanconi Anaemia and Nijmegen Breakage Syndrome. In: Lankenau, DH. (eds) Genome Integrity. Genome Dynamics and Stability, vol 1. Springer, Berlin, Heidelberg . https://doi.org/10.1007/7050_013

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