Chapter 28 : Additional Diseases Associated with Defective Responses to DNA Damage

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This chapter examines two genetic disorders, each exhibiting locus heterogeneity and each representing the biological consequences of mutations in different genes in a specific DNA repair pathway. Both of these disorders present with a significant cancer predisposition and have associated cellular characteristics reflective of inherent chromosome instability. However, experimental approaches to the identification and characterization of the underlying genetics have taken strikingly different paths. The first of these disorders, hereditary nonpolyposis colon cancer (HNPCC), results from mutations in different genes associated with DNA mismatch repair (MMR). Given that MMR had been extensively studied before its connection to HNPCC was established, more recent studies have focused on evaluating additional MMR candidate genes for mutations in patients with HNPCC and elucidation of the biological basis for the organ-specific nature of the disorder. In contrast, the second disease considered in this chapter, is a disorder represented by multiple complementation groups that all exhibit defects in cross-link repair and responses to oxidative damage. These are not repair functions that are well defined or representative of established biochemical pathways. Therefore, experimental approaches have focused on the identification of the different genes responsible for FA and characterization of how the proteins involved define a unique biological pathway.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Additional Diseases Associated with Defective Responses to DNA Damage, p 979-999. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch28

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Tumor Necrosis Factor alpha
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Image of Figure 28–1
Figure 28–1

An extended pedigree consistent with a diagnosis of HNPCC brought to light following cancer diagnosis in the proband (arrow). Squares denote males and circles denote females, with a slash to identify deceased family members. Age at death (d) is given below each patient who died, with Inf indicating infancy. Open symbols are unaffected family members, while bicolored symbols identify individuals with multiple primary cancers. Squares or circles with numbers denote the number of unaffected male or female progeny, and combined symbols containing numbers denote the number of unaffected progeny of both sexes. Primary cancer and the age at diagnosis are shown below the symbols, and the bottom-most number is the current age or the age at death.(Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Additional Diseases Associated with Defective Responses to DNA Damage, p 979-999. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch28
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Image of Figure 28–2
Figure 28–2

DNA polymerase slippage. Depicted are both the normal replication product and the result of strand slippage following a second round of DNA replication. (Adapted from http://www.nottingham.ac.uk/microbiology/.)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Additional Diseases Associated with Defective Responses to DNA Damage, p 979-999. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch28
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Image of Figure 28–3
Figure 28–3

H6 cells are defective in the repair of (GT)•(CA) and (GT)•(CA) heteroduplexes. (GT)•(CA) and (GT)•(CA) heteroduplexes and (GT)•(CA) and (GT)•(CA) homoduplexes were subjected to MMR by nuclear extracts of H6 cells (see the text) and of SO cells (see the text). BLNK indicates no extract. Strand specificity was provided by incision of the complementary or viral strands at Sau961 or gpII sites, respectively. After the reaction, the repeated sequence elements were excised from the reaction products by cleavage at flanking restriction enzyme sites and then separated by electrophoresis. The products were visualized by hybridization with strand-specific probes.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Additional Diseases Associated with Defective Responses to DNA Damage, p 979-999. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch28
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Image of Figure 28–4
Figure 28–4

Putative role of mutations in MMR genes. A mutation in one MMR gene leads to reduced MMR function due to haploinsufficiency, which promotes mutations in traditional genes, such as the adenomatous polyposis coli gene and K Genes with coding microsatellites accumulate frameshift mutations and lose function, leading to cancer. The target genes likely dictate the organ specificity of HNPCC. The approximate percentages of all colorectal cancers with MMR deficiency that harbor these frameshift mutations are shown at the top. The three MMR genes that have coding microsatellites are shown at the bottom. β denotes transforming growth factor β1 receptor II, denotes retinoblastoma protein-interacting zinc finger, denotes transcription factor 4, denotes BCL-2-associated X, denotes insulin-like growth factor II receptor, and denotes deleted in colorectal cancer. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Additional Diseases Associated with Defective Responses to DNA Damage, p 979-999. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch28
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Image of Figure 28–5
Figure 28–5

FA cell sensitivity. (A) Cells from patients with FA are typically hypersensitive to treatment with agents such as mitomycin (MMC) that result in the formation of interstrand crosslinks in DNA. (B) Cells from certain FA genetic complementation groups also show a defect in the removal of cross-links from DNA.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Additional Diseases Associated with Defective Responses to DNA Damage, p 979-999. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch28
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Image of Figure 28–6
Figure 28–6

FA cells from genetic complementation group A (B) are defective in the recovery of normal rates of semiconservative DNA synthesis after exposure to psoralen plus 365-nm radiation. Normal cells and FA cells from genetic complementation group B are shown in panels A and C, respectively.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Additional Diseases Associated with Defective Responses to DNA Damage, p 979-999. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch28
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Figure 28–7

Homozygosity mapping of the FANCG gene. Homozygosity mapping of 269 microsatellite markers spaced at 11-cM intervals in an FA family is shown. Each box represents a microsatellite marker located on the 22 autosomes identified by number; gold boxes indicate markers that were informative and homozygous in both affected children, a result that would be consistent with linkage; shaded boxes indicate markers that were homozygous in both affected children but not informative; white boxes indicate markers that were heterozygous in at least one of the two affected children; missing boxes indicate markers that were not analyzed. (Adapted from reference .)

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Additional Diseases Associated with Defective Responses to DNA Damage, p 979-999. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch28
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Figure 28–8

The FA-BRCA pathway. Several FA proteins, including A, B, C, E, F, G, and L, form a complex in the nuclei of normal human cells. In response to DNA damage, or during the S phase of the cell cycle, this complex mediates the monoubiquitination (Ub) of FANCD2 atlysine 561 (K561). Activated FANCD2, in turn, is translocated to chromatin and DNA repair foci containing the BRCA1 protein and the BRCA2-FANCD1 protein complex.

Citation: Errol C, Graham C, Wolfram S, Richard D, Roger A, Tom E. 2006. Additional Diseases Associated with Defective Responses to DNA Damage, p 979-999. In DNA Repair and Mutagenesis, Second Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816704.ch28
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1. Aaltonen, L. A.,, P. Peltomaki,, F. S. Leach,, P. Sistonen,, L. Pylkkanen,, J. P. Mecklin,, H. Jarvinen,, S. M. Powell,, J. Jen,, S. R. Hamilton,, G. M. Petersen,, K. W. Kinzler,, A. Delachapelle, and, B. Vogelstein. 1993. Clues to the pathogenesis of familial colorectal cancer. Science 260:812816.
2. Aarnio, M.,, R. Sankila,, E. Pukkala,, R. Salovaara,, L. A. Aaltonen,, A. de la Chapelle,, P. Peltomaki,, J. P. Mecklin, and, H. J. Jarvinen. 1999. Cancer risk in mutation carriers of DNA–mismatch–repair genes. Int. J. Cancer 81:214218.
3. Abu–Issa, R.,, G. Eichele, and, H. Youssoufian. 1999. Expression of the Fanconi anemia group A gene (Fanca) during mouse embryogenesis. Blood 94:818824.
4. Akiyama, Y.,, H. Sato,, T. Yamada,, H. Nagasaki,, A. Tsuchiya,, R. Abe, and, Y. Yuasa. 1997. Germ–line mutation of the hMSH6/GTBP gene in an atypical hereditary nonpolyposis colorectal cancer kindred. Cancer Res. 57:39203923.
5. Allen, B. A., and, J. P. Terdiman. 2003. Hereditary polyposis syndromes and hereditary non–polyposis colorectal cancer. Best Pract. Res. Clin. Gastroenterol. 17:237258.
6. Alter, B. P., 2003. Cancer in Fanconi anemia, 1927–2001. Cancer 97:425440.
7. Auerbach, A. D., and, S. R. Wolman. 1978. Carcinogen–induced chromosome breakage in Fanconi’s anaemia heterozygous cells. Nature 271:6971.
8. Auerbach, A. D., and, S. R. Wolman. 1976. Susceptibility of Fanconi’s anaemia fibroblasts to chromosome damage by carcinogens. Nature 261:494496.
9. Bagby, G. C., Jr.,, G. M. Segal,, A. D. Auerbach,, T. Onega,, W. Keeble, and, M. C. Heinrich. 1993. Constitutive and induced expression of hematopoietic growth factor genes by fibroblasts from children with Fanconi anemia. Exp. Hematol. 21:14191426.
10. Baker, S. M.,, C. E. Bronner,, L. Zhang,, A. W. Plug,, M. Robatzek,, G. Warren,, E. A. Elliott,, J. Yu,, T. Ashley,, N. Arnheim,, R. A. Flavell, and, R. M. Liskay. 1995. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 82:309319.
11. Baker, S. M.,, A. W. Plug,, T. A. Prolla,, C. E. Bronner,, A. C. Harris,, X. Yao,, D. M. Christie,, C. Monell,, N. Arnheim,, A. Bradley,, T. Ashley, and, R. M. Liskay. 1996. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat. Genet. 13:336342.
12. Baranger, L.,, M. Gardembas,, J. Hillion,, C. Foussard,, N. Ifrah,, M. Boasson, and, R. Berger. 1993. Rearrangements of the RARA and PML genes in a cytogenetic variant of acute promyelocytic leukemia. Genes Chromosomes Cancer 6:118120.
13. Baranovskaya, S.,, J. L. Soto,, M. Perucho, and, S. R. Malkhosyan. 2001. Functional significance of concomitant inactivation of hMLH1 and hMSH6 in tumor cells of the microsatellite mutator phenotype. Proc. Natl. Acad. Sci. USA 98:1510715112.
14. Battaile, K. P.,, R. L. Bateman,, D. Mortimer,, J. Mulcahy,, R. K. Rathbun,, G. Bagby,, W. H. Fleming, and, M. Grompe. 1999. In vivo selec– tion of wild–type hematopoietic stem cells in a murine model of Fanconi anemia. Blood 94:21512158.
15. Beckman, J. S., and, J. L. Weber. 1992. Survey of human and rat microsatellites. Genomics 12:627631.
16. Berends, M. J.,, Y. Wu,, R. H. Sijmons,, R. G. Mensink,, T. van der Sluis,, J. M. Hordijk–Hos,, E. G. de Vries,, H. Hollema,, A. Karrenbeld,, C. H. Buys,, A. G. van der Zee,, R. M. Hofstra, and, J. H. Kleibeuker. 2002. Molecular and clinical characteristics of MSH6 variants: an analysis of 25 index carriers of a germline variant. Am. J. Hum. Genet. 70:2637.
17. Berger, R.,, M. Le Coniat, and, M. C. Gendron. 1993. Fanconi anemia. Chromosome breakage and cell cycle studies. Cancer Genet. Cytogenet. 69:1316.
18. Brezden–Masley, C.,, M. D. Aronson,, B. Bapat,, A. Pollett,, R. Gryfe,, M. Redston, and, S. Gallinger. 2003. Hereditary nonpolyposis colorectal cancer—molecular basis. Surgery 134:2933.
19. Bronner, C. E.,, S. M. Baker,, P. T. Morrison,, G. Warren,, L. G. Smith,, M. K. Lescoe,, M. Kane,, C. Earabino,, J. Lipford,, A. Lindblom,, P. Tannergard,, R. J. Bollag,, A. R. Godwin,, D. C. Ward,, M. Nordenskjold,, R. Fishel,, R. Kolodner, and, R. M. Liskay. 1994. Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non–polyposis colon cancer. Nature 368:258261.
20. Busch, D. B.,, M. Z. Zdzienicka,, A. T. Natarajan,, N. J. Jones,, W. J. Overkamp,, A. Collins,, D. L. Mitchell,, M. Stefanini,, E. Botta,, R. B. Albert,, N. Liu,, D. A. White,, A. J. van Gool, and, L. H. Thompson. 1996. A CH0 mutant, UV40, that is sensitive to diverse mutagens and represents a new complementation group of mitomycin C sensitivity. Mutat. Res. 363:209221.
21. Carreau, M., and, M. Buchwald. 1998. The Fanconi anemia genes. Curr. Opin. Pediatr. 10:6569.
22. Carreau, M.,, O. I. Gan,, L. Liu,, M. Doedens,, C. McKerlie,, J. E. Dick, and, M. Buchwald. 1998. Bone marrow failure in the Fanconi anemia group C mouse model after DNA damage. Blood 91:27372744.
23. Caskey, C. T.,, A. Pizzuti,, Y. H. Fu,, R. G. Fenwick, Jr., and, D. L. Nelson. 1992. Triplet repeat mutations in human disease. Science 256:784789.
24. Centra, M.,, E. Memeo,, M. d’Apolito,, M. Savino,, L. Ianzano,, A. Notarangelo,, J. Liu,, N. A. Doggett,, L. Zelante, and, A. Savoia. 1998. Fine exon–intron structure of the Fanconi anemia group A (FAA) gene and characterization of two genomic deletions. Genomics 51:463467.
25. Chen, M.,, D. J. Tomkins,, W. Auerbach,, C. McKerlie,, H. Yous–soufian,, L. Liu,, O. Gan,, M. Carreau,, A. Auerbach,, T. Groves,, C. J. Guidos,, M. H. Freedman,, J. Cross,, D. H. Percy,, J. E. Dick,, A. L. Joyner, and, M. Buchwald. 1996. Inactivation of Fac in mice produces inducible chromosomal instability and reduced fertility reminiscent of Fanconi anaemia. Nat. Genet. 12:448451.
26. Cumming, R. C.,, J. Lightfoot,, K. Beard,, H. Youssoufian,, P. J. O’Brien, and, M. Buchwald. 2001. Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1. Nat. Med. 7:814820.
27. D’Andrea, A. D., 1996. Fanconi anaemia forges a novel pathway. Nat. Genet. 14:240242.
28. D’Andrea, A. D., 2003. The Fanconi Anemia/BRCA signaling pathway: disruption in cisplatin–sensitive ovarian cancers. Cell Cycle 2:290292.
29. D’Andrea, A. D., 2003. The Fanconi road to cancer. Genes Dev. 17:19331936.
30. Dean, S. W.,, H. R. Sykes, and, A. R. Lehmann. 1988. Inactivation by nitrogen mustard of plasmids introduced into normal and Fanconi’s anaemia cells. Mutat Res. 194:5763.
31. Deininger, P. L., and, M. A. Batzer. 1999. Alu repeats and human disease. Mol. Genet. Metab. 67:183193.
32. De Rosa, M.,, C. Fasano,, L. Panariello,, M. I. Scarano,, G. Belli,, A. Iannelli,, F. Ciciliano, and, P. Izzo. 2000. Evidence for a recessive inheritance of Turcot’s syndrome caused by compound heterozygous mutations within the PMS2 gene. Oncogene 19:17191723.
33. de Vries, S. S.,, E. B. Baart,, M. Dekker,, A. Siezen,, D. G. de Rooij,, P. de Boer, and, H. te Riele. 1999. Mouse MutS–like protein Msh5 is required for proper chromosome synapsis in male and female meiosis. Genes Dev. 13:523531.
34. de Wind, N.,, M. Dekker,, A. Berns,, M. Radman, and, H. te Riele. 1995. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell 82:321330.
35. de Wind, N.,, M. Dekker,, N. Claij,, L. Jansen,, Y. van Klink,, M. Rad–man,, G. Riggins,, M. van der Valk,, K. van’t Wout, and, H. te Riele. 1999. HNPCC–like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch–repair protein functions. Nat. Genet. 23:359362.
36. de Wind, N.,, M. Dekker,, A. van Rossum,, M. van der Valk, and, H. te Riele. 1998. Mouse models for hereditary nonpolyposis colorectal cancer. Cancer Res. 58:248255.
37. de Winter, J. P.,, F. Leveille,, C. G. van Berkel,, M. A. Rooimans,, L. van Der Weel,, J. Steltenpool,, I. Demuth,, N. V. Morgan,, N. Alon,, L. Bosnoyan–Collins,, J. Lightfoot,, P. A. Leegwater,, Q. Waisfisz,, K. Komatsu,, F. Arwert,, J. C. Pronk,, C. G. Mathew,, M. Digweed,, M. Buchwald, and, H. Joenje. 2000. Isolation of a cDNA representing the Fanconi anemia complementation group E gene. Am. J. Hum. Genet. 67:13061308.
38. de Winter, J. P.,, M. A. Rooimans,, L. van Der Weel,, C. G. van Berkel,, N. Alon,, L. Bosnoyan–Collins,, J. de Groot,, Y. Zhi,, Q. Waisfisz,, J. C. Pronk,, F. Arwert,, C. G. Mathew,, R. J. Scheper,, M. E. Hoatlin,, M. Buchwald, and, H. Joenje. 2000. The Fanconi anaemia gene FANCF encodes a novel protein with homology to ROM. Nat. Genet. 24:1516.
39. de Winter, J. P.,, L. van der Weel,, J. de Groot,, S. Stone,, Q. Wais–fisz,, F. Arwert,, R. J. Scheper,, F. A. Kruyt,, M. E. Hoatlin, and, H. Joenje. 2000. The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Hum. Mol. Genet. 9:26652674.
40. de Winter, J. P.,, Q. Waisfisz,, M. A. Rooimans,, C. G. van Berkel,, L. Bosnoyan–Collins,, N. Alon,, M. Carreau,, O. Bender,, I. Demuth,, D. Schindler,, J. C. Pronk,, F. Arwert,, H. Hoehn,, M. Digweed,, M. Buchwald, and, H. Joenje., 1998. The Fanconi anaemia group G gene FANCG is identical with XRCC9. Nat. Genet. 20:281283.
41. Duckworth–Rysiecki, G.,, K. Cornish,, C. A. Clarke, and, M. Buch–wald. 1985. Identification of two complementation groups in Fanconi anemia. Somatic Cell. Mol. Genet. 11:3541.
42. Dutrillaux, B.,, A. Aurias,, A. M. Dutrillaux,, D. Buriot, and, M. Prieur. 1982. The cell cycle of lymphocytes in Fanconi anemia. Hum. Genet. 62:327332.
43. Duval, A.,, S. Rolland,, A. Compoint,, E. Tubacher,, B. Iacopetta,, G. Thomas, and, R. Hamelin. 2001. Evolution of instability at coding and non–coding repeat sequences in human MSI–H colorectal cancers. Hum. Mol. Genet. 10:513518.
44. Edelmann, W.,, P. E. Cohen,, M. Kane,, K. Lau,, B. Morrow,, S. Bennett,, A. Umar,, T. Kunkel,, G. Cattoretti,, R. Chaganti,, J. W. Pollard,, R. D. Kolodner, and, R. Kucherlapati. 1996. Meiotic pachytene arrest in MLH1–deficient mice. Cell 85:11251134.
45. Edelmann, W.,, P. E. Cohen,, B. Kneitz,, N. Winand,, M. Lia,, J. Heyer,, R. Kolodner,, J. W. Pollard, and, R. Kucherlapati. 1999. Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nat. Genet. 21:123127.
46. Edelmann, W.,, A. Umar,, K. Yang,, J. Heyer,, M. Kucherlapati,, M. Lia,, B. Kneitz,, E. Avdievich,, K. Fan,, E. Wong,, G. Crouse,, T. Kunkel,, M. Lipkin,, R. D. Kolodner, and, R. Kucherlapati. 2000. The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression. Cancer Res. 60:803807.
47. Edelmann, W.,, K. Yang,, A. Umar,, J. Heyer,, K. Lau,, K. Fan,, W. Liedtke,, P. E. Cohen,, M. F. Kane,, J. R. Lipford,, N. Yu,, G. F. Crouse,, J. W. Pollard,, T. Kunkel,, M. Lipkin,, R. Kolodner, and, R. Kucherlapati. 1997. Mutation in the mismatch repair gene Msh6 causes cancer susceptibility. Cell 91:467477.
48. Faivre, L.,, P. Guardiola,, C. Lewis,, I. Dokal,, W. Ebell,, A. Zatterale,, C. Altay,, J. Poole,, D. Stones,, M. L. Kwee,, M. van Weel–Sipman,, C. Havenga,, N. Morgan,, J. de Winter,, M. Digweed,, A. Savoia,, J. Pronk,, T. de Ravel,, S. Jansen,, H. Joenje, et al., for the European Fanconi Anemia Research Group., 2000. Association of complementation group and mutation type with clinical outcome in Fanconi anemia. Blood 96:40644070.
49. Fanconi, G., 1927. Familiaere infantile perniziosaartige Anaemie (pernizioeses Blutbild und Konstitution). Jahrb. Kinderheilk. 117:257280.
50. Fanconi, G., 1967. Familial constitutional panmyelocytopathy, Fanconi’s anemia (F.A.). I. Clinical aspects. Semin. Hematol. 4:233240.
51. Fanconi Anaemia/Breast Cancer Consortium., 1996. Positional cloning of the Fanconi anaemia group A gene. Nat. Genet. 14:324328.
52. Fishel, R.,, M. K. Lescoe,, M. R. Rao,, N. G. Copeland,, N. A. Jenkins,, J. Garber,, M. Kane, and, R. Kolodner. 1993. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75:10271038.
53. Fornace, A. J., Jr.,, J. B. Little, and, R. R. Weichselbaum. 1979. DNA repair in a Fanconi’s anemia fibroblast cell strain. Biochim. Biophys. Acta 561:99109.
54. Friedberg, E. C.,, J. Awbrey, and, H. K. Hagler. 2002. Database of mouse strains carrying targeted mutations in genes affecting cellular responses to DNA damage. Version 4. [Online.] "http://pathcuric1.swmed.edu/ research/research.htm".
55. Friedberg, E. C.,, G. C. Walker, and, W. Siede. 1995. DNA Repair and Mutagenesis. ASM Press, Washington, D.C.
56. Fujiwara, Y., 1982. Defective repair of mitomycin C crosslinks in Fanconi’s anemia and loss in confluent normal human and xeroderma pigmentosum cells. Biochim. Biophys. Acta 699:217225.
57. Fujiwara, Y.,, Y. Kano, and, Y. Yamamoto. 1984. DNA interstrand cross–linking, repair, and SCE mechanism in human cells in special reference to Fanconi anemia. Basic Life Sci. 29:787800.
58. Fujiwara, Y., and, M. Tatsumi. 1977. Cross–link repair in human cells and its possible defect in Fanconi’s anemia cells. J. Mol. Biol. 113:635649.
59. Garcia–Higuera, I.,, Y. Kuang,, J. Denham, and, A. D. D’Andrea. 2000. The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex. Blood 96:32243230.
60. Garcia–Higuera, I.,, Y. Kuang,, D. Naf,, J. Wasik, and, A. D. D’Andrea. 1999. Fanconi anemia proteins FANCA, FANCC, and FANCG/XRCC9 interact in a functional nuclear complex. Mol. Cell. Biol. 19:48664873.
61. Garcia–Higuera, I.,, T. Taniguchi,, S. Ganesan,, M. S. Meyn,, C. Timmers,, J. Hejna,, M. Grompe, and, A. D. D’Andrea. 2001. Interaction of the Fanconi anemia proteins and BRCA1 in a common pathway. Mol. Cell 7:249262.
62. Garriga, S., and, W. H. Crosby. 1959. The incidence of leukemia in families of patients with hypoplasia of the marrow. Blood 14:10081014.
63. Gavish, H.,, C. C. dos Santos, and, M. Buchwald. 1993. A Leu554–to–Pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein. Hum. Mol. Genet. 2:123126.
64. German, J., 1972. Genes which increase chromosomal instability in somatic cells and predispose to cancer. Prog. Med. Genet. 8:61101.
65. Gillio, A. P.,, P. C. Verlander,, S. D. Batish,, P. F. Giampietro, and, A. D. Auerbach. 1997. Phenotypic consequences of mutations in the Fanconi anemia FAC gene: an International Fanconi Anemia Registry study. Blood 90:105110.
66. Grady, W. M.,, A. Rajput,, L. Myeroff,, D. F. Liu,, K. Kwon,, J. Willis, and, S. Markowitz. 1998. Mutation of the type II transforming growth factor–beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas. Cancer Res. 58:31013104.
67. Hamilton, S. R.,, B. Liu,, R. E. Parsons,, N. Papadopoulos,, J. Jen,, S. M. Powell,, A. J. Krush,, T. Berk,, Z. Cohen,, B. Tetu,, P. C. Burger,, P. A. Wood,, F. Taqi,, S. V. Booker,, G. M. Petersen,, G. J. A. Offerhaus,, A. C. Tersmette,, F. M. Giardiello,, B. Vogelstein, and, K. W. Kinzler. 1995. The molecular basis of Turcot’s syndrome. N. Engl. J. Med. 332:839847.
68. Haneline, L. S.,, H. E. Broxmeyer,, S. Cooper,, G. Hangoc,, M. Carreau,, M. Buchwald, and, D. W. Clapp. 1998. Multiple inhibitory cytokines induce deregulated progenitor growth and apoptosis in hematopoietic cells from Fac–/– mice. Blood 91:40924098.
69. Hang, B.,, A. T. Yeung, and, M. W. Lambert. 1993. A damage–recognition protein which binds to DNA containing interstrand cross–links is absent or defective in Fanconi anemia, complementation group A, cells. Nucleic Acids Res. 21:41874192.
70. Hejna, J. A.,, C. D. Timmers,, C. Reifsteck,, D. A. Bruun,, L. W. Lucas,, P. M. Jakobs,, S. Toth–Fejel,, N. Unsworth,, S. L. Clemens,, D. K. Garcia,, S. L. Naylor,, M. J. Thayer,, S. B. Olson,, M. Grompe, and, R. E. Moses. 2000. Localization of the Fanconi anemia complementation group D gene to a 200–kb region on chromosome 3p25.3. Am. J. Hum. Genet. 66:15401551.
71. Hirsch, B.,, A. Shimamura,, L. Moreau,, S. Baldinger,, M. Hagalshiekh,, B. Bostrom,, S. Sencer, and, A. D. D’Andrea. 2004. Association of biallelic BRCA2/FANCD1 mutations with spontaneous chromosomal instability and solid tumors of childhood. Blood 103:25542559.
72. Hoehn, H.,, H. Koch,, J. Kohler,, T. Bettecken,, M. Kubbies,, W. Heckl,, D. Salk, and, P. S. Rabinovitch. 1987. Interphase cell flow cytometry as a means of monitoring genomic size in normal and neoplastoid cell cultures. Cancer Genet. Cytogenet. 24:191204.
73. Hoshino, T.,, J. Wang,, M. P. Devetten,, N. Iwata,, S. Kajigaya,, R. J. Wise,, J. M. Liu, and, H. Youssoufian. 1998. Molecular chaperone GRP94 binds to the Fanconi anemia group C protein and regulates its intracellular expression. Blood 91:43794386.
74. Houghtaling, S.,, C. Timmers,, M. Noll,, M. J. Finegold,, S. N. Jones,, M. S. Meyn, and, M. Grompe. 2003. Epithelial cancer in Fanconi anemia complementation group D2 (Fancd2) knockout mice. Genes Dev. 17:20212035.
75. Howlett, N. G.,, T. Taniguchi,, S. Olson,, B. Cox,, Q. Waisfisz,, C. De Die–Smulders,, N. Persky,, M. Grompe,, H. Joenje,, G. Pals,, H. Ikeda,, E. A. Fox, and, A. D. D’Andrea. 2002. Biallelic inactivation of BRCA2 in Fanconi anemia. Science 297:606609.
76. Ianzano, L.,, M. D’Apolito,, M. Centra,, M. Savino,, O. Levran,, A. D. Auerbach,, A. M. Cleton–Jansen,, N. A. Doggett,, J. C. Pronk,, A. J. Tipping,, R. A. Gibson,, C. G. Mathew,, S. A. Whitmore,, S. Apostolou,, D. F. Callen,, L. Zelante, and, A. Savoia. 1997. The genomic organization of the Fanconi anemia group A (FAA) gene. Genomics 41:309314.
77. Ionov, Y.,, M. A. Peinado,, S. Malkhosyan,, D. Shibata, and, M. Perucho. 1993. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 363:558561.
78. Jacob, S., and, F. Praz. 2002. DNA mismatch repair defects: role in colorectal carcinogenesis. Biochimie 84:2747.
79. Jiricny, J., 1994. Colon cancer and DNA repair: have mismatches met their match? Trends Genet. 10:164168.
80. Joenje, H.,, M. Levitus,, Q. Waisfisz,, A. D’A ndrea,, I. Garcia–Higuera,, T. Pearson,, C. G. van Berkel,, M. A. Rooimans,, N. Morgan,, C. G. Mathew, and, F. Arwert. 2000. Complementation analysis in Fanconi anemia: assignment of the reference FA–H patient to group A. Am. J. Hum. Genet. 67:759762.
81. Kato, H., and, H. F. Stich. 1976. Sister chromatid exchanges in ageing and repair–deficient human fibroblasts. Nature 260:447448.
82. Kawate, H.,, K. Sakumi,, T. Tsuzuki,, Y. Nakatsuru,, T. Ishikawa,, S. Takahashi,, H. Takano,, T. Noda, and, M. Sekiguchi. 1998. Separation of killing and tumorigenic effects of an alkylating agent in mice defective in two of the DNA repair genes. Proc. Natl. Acad. Sci. USA 95:51165120.
83. Kaye, J.,, C. A. Smith, and, P. C. Hanawalt. 1980. DNA repair in human cells containing photoadducts of 8–methoxypsoralen or angelicin. Cancer Res. 40:696702.
84. Klocker, H.,, B. Auer,, M. Hirsch–Kauffmann,, H. Altmann,, H. J. Burtscher, and, M. Schweiger. 1983. DNA repair dependent NAD+ metabolism is impaired in cells from patients with Fanconi’s anemia. EMBO J. 2:303307.
85. Kneitz, B.,, P. E. Cohen,, E. Avdievich,, L. Zhu,, M. F. Kane,, H. Hou, Jr.,, R. D. Kolodner,, R. Kucherlapati,, J. W. Pollard, and, W. Edelmann. 2000. MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Genes Dev. 14:10851097.
86. Koc, A.,, J. C. Pronk,, M. Alikasifoglu,, H. Joenje, and, C. Altay. 1999. Variable pathogenicity of exon 43del (FAA) in four Fanconi anaemia patients within a consanguineous family. Br. J. Haematol. 104:127130.
87. Koomen, M.,, N. C. Cheng,, H. J. van de Vrugt,, B. C. Godthelp,, M. A. van der Valk,, A. B. Oostra,, M. Z. Zdzienicka,, H. Joenje, and, F. Arwert. 2002. Reduced fertility and hypersensitivity to mitomycin C characterize Fancg/Xrcc9 null mice. Hum. Mol. Genet. 11:273281.
88. Kruse, R.,, A. Rutten,, C. Lamberti,, H. R. Hosseiny–Malayeri,, Y. Wang,, C. Ruelfs,, M. Jungck,, M. Mathiak,, T. Ruzicka,, W. Hartschuh,, M. Bisceglia,, W. Friedl, and, P. Propping. 1998. Muir–Torre phenotype has a frequency of DNA mismatch–repair–gene mutations similar to that in hereditary nonpolyposis colorectal cancer families defined by the Amsterdam criteria. Am. J. Hum. Genet. 63:6370.
89. Kruyt, F. A.,, T. Hoshino,, J. M. Liu,, P. Joseph,, A. K. Jaiswal, and, H. Youssoufian. 1998. Abnormal microsomal detoxification implicated in Fanconi anemia group C by interaction of the FAC protein with NADPH cytochrome P450 reductase. Blood 92:30503056.
90. Kuhl, D. P., and, C. T. Caskey. 1993. Trinucleotide repeats and genome variation. Curr. Opin. Genet. Dev. 3:404407.
91. Kunkel, T. A., 1993. Nucleotide repeats. Slippery DNA and diseases. Nature 365:207208.
92. Kupfer, G. M.,, T. Yamashita,, D. Naf,, A. Suliman,, S. Asano, and, A. D. D’Andrea. 1997. The Fanconi anemia polypeptide, FAC, binds to the cyclin–dependent kinase, cdc2. Blood 90:10471054.
93. Laken, S. J.,, G. M. Petersen,, S. B. Gruber,, C. Oddoux,, H. Ostrer,, F. M. Giardiello,, S. R. Hamilton,, H. Hampel,, A. Markowitz,, D. Klimstra,, S. Jhanwar,, S. Winawer,, K. Offit,, M. C. Luce,, K. W. Kinzler, and, B. Vogelstein. 1997. Familial colorectal cancer in Ashkenazim due to a hyper– mutable tract in APC. Nat. Genet. 17:7983.
94. Lambert, M. W.,, G. J. Tsongalis,, W. C. Lambert,, B. Hang, and, D. D. Parrish. 1992. Defective DNA endonuclease activities in Fanconi’s anemia cells, complementation groups A and B. Mutat Res. 273:5771.
95. Leach, F. S.,, N. C. Nicolaides,, N. Papadopoulos,, B. Liu,, J. Jen,, R. Parsons,, P. Peltomaki,, P. Sistonen,, L. A. Aaltonen,, M. Nystrom–Lahti, et al., 1993. Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:12151225.
96. Levitus, M.,, M. A. Rooimans,, J. Steltenpool,, N. F. Cool,, A. B. Oostra,, C. G. Mathew,, M. E. Hoatlin,, Q. Waisfisz,, F. Arwert,, J. P. de Winter, and, H. Joenje. 2004. Heterogeneity in Fanconi anemia: evidence for 2 new genetic subtypes. Blood 103:24982503.
97. Levran, O.,, N. A. Doggett, and, A. D. Auerbach. 1998. Identification of Alu–mediated deletions in the Fanconi anemia gene FAA. Hum. Mutat. 12:145152.
98. Lindblom, A.,, P. Tannergard,, B. Werelius, and, M. Nordenskjold. 1993. Genetic mapping of a second locus predisposing to hereditary non–polyposis colon cancer. Nat. Genet. 5:279282.
99. Liu, J. M.,, N. S. Young,, C. E. Walsh,, M. Cottler–Fox,, C. Carter,, C. Dunbar,, A. J. Barrett, and, R. Emmons. 1997. Retroviral mediated gene transfer of the Fanconi anemia complementation group C gene to hematopoietic progenitors of group C patients. Hum. Gene Ther. 8:17151730.
100. Lo Ten Foe, J. R.,, M. A. Rooimans,, L. Bosnoyan–Collins,, N. Alon,, M. Wijker,, L. Parker,, J. Lightfoot,, M. Carreau,, D. F. Callen,, A. Savoia,, N. C. Cheng,, C. G. van Berkel,, M. H. Strunk,, J. J. Gille,, G. Pals,, F. A. Kruyt,, J. C. Pronk,, F. Arwert,, M. Buchwald, and, H. Joenje. 1996. Expression cloning of a cDNA for the major Fanconi anaemia gene, FAA. Nat. Genet. 14:320323.
101. Loukola, A.,, S. Vilkki,, J. Singh,, V. Launonen, and, L. A. Aaltonen. 2000. Germline and somatic mutation analysis of MLH3 in MSI–positive colorectal cancer. Am. J. Pathol. 157:347352.
102. Lynch, H. T., and, A. de la Chapelle. 1999. Genetic susceptibility to non–polyposis colorectal cancer. J. Med. Genet. 36:801818.
103. Lynch, H. T., and, A. de la Chapelle. 2003. Hereditary colorectal cancer. N. Engl. J. Med. 348:919932.
104. Lynch, H. T.,, T. C. Smyrk,, P. Watson,, S. J. Lanspa,, J. F. Lynch,, P. M. Lynch,, R. J. Cavalieri, and, C. R. Boland. 1993. Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 104:15351549.
105. Matsumoto, A.,, J. M. Vos, and, P. C. Hanawalt. 1989. Repair analysis of mitomycin C–induced DNA crosslinking in ribosomal RNA genes in lymphoblastoid cells from Fanconi’s anemia patients. Mutat. Res. 217:185192.
106. McAllister, K. A.,, L. M. Bennett,, C. D. Houle,, T. Ward,, J. Mal– phurs,, N. K. Collins,, C. Cachafeiro,, J. Haseman,, E. H. Goulding,, D. Bunch,, E. M. Eddy,, B. J. Davis, and, R. W. Wiseman. 2002. Cancer susceptibility of mice with a homozygous deletion in the COOH–terminal domain of the Brca2 gene. Cancer Res. 62:990994.
107. Medhurst, A. L.,, P. A. Huber,, Q. Waisfisz,, J. P. de Winter, and, C. G. Mathew. 2001. Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway. Hum. Mol. Genet. 10:423429.
108. Meetei, A. R.,, J. P. de Winter,, A. L. Medhurst,, M. Wallisch,, Q. Waisfisz,, H. J. van de Vrugt,, A. B. Oostra,, Z. Yan,, C. Ling,, C. E. Bishop,, M. E. Hoatlin,, H. Joenje, and, W. Wang. 2003. A novel ubiquitin ligase is deficient in Fanconi anemia. Nat. Genet. 35:165170.
109. Meetei, A. R.,, M. Levitus,, Y. Xue,, A. L. Medhurst,, M. Zwaan,, C. Ling,, M. A. Rooimans,, P. Bier,, M. Hoatlin,, G. Pals,, J. P. de Winter,, W. Wang, and, H. Joenje. 2004. X–linked inheritance of Fanconi anemia complementation group B. Nat. Genet. 36:12191224.
110. Meetei, A. R.,, S. Sechi,, M. Wallisch,, D. Yang,, M. K. Young,, H. Joenje,, M. E. Hoatlin, and, W. Wang. 2003. A multiprotein nuclear complex connects Fanconi anemia and Bloom syndrome. Mol. Cell. Biol. 23:34173426.
111. Miyaki, M.,, J. Nishio,, M. Konishi,, R. Kikuchi–Yanoshita,, K. Tanaka,, M. Muraoka,, M. Nagato,, J. M. Chong,, M. Koike,, T. Terada,, Y. Kawahara,, A. Fukutome,, J. Tomiyama,, Y. Chuganji,, M. Momoi, and, J. Utsunomiya. 1997. Drastic genetic instability of tumors and normal tissues in Turcot syndrome. Oncogene 15:28772881.
112. Moustacchi, E., and, C. Diatloff–Zito. 1985. DNA semi–conservative synthesis in normal and Fanconi anemia fibroblasts following treatment with 8–methoxypsoralen and near ultraviolet light or with X–rays. Hum. Genet. 70:236242.
113. Moustacchi, E.,, D. Papadopoulo,, C. Diatloff–Zito, and, M. Buch–wald. 1987. Two complementation groups of Fanconi’s anemia differ in their phenotypic response to a DNA–crosslinking treatment. Hum. Genet. 75:4547.
114. Naf, D.,, G. M. Kupfer,, A. Suliman,, K. Lambert, and, A. D. D’Andrea. 1998. Functional activity of the Fanconi anemia protein FAA requires FAC binding and nuclear localization. Mol. Cell. Biol. 18:59525960.
115. Nakanishi, K.,, T. Taniguchi,, V. Ranganathan,, H. V. New,, L. A. Moreau,, M. Stotsky,, C. G. Mathew,, M. B. Kastan,, D. T. Weaver, and, A. D. D’Andrea. 2002. Interaction of FANCD2 and NBS1 in the DNA damage response. Nat. Cell Biol. 4:913920.
116. Noll, M.,, R. L. Bateman,, A. D. D’Andrea, and, M. Grompe. 2001. Preclinical protocol for in vivo selection of hematopoietic stem cells corrected by gene therapy in Fanconi anemia group C. Mol. Ther. 3:1423.
117. Noll, M.,, K. P. Battaile,, R. Bateman,, T. P. Lax,, K. Rathbun,, C. Reifsteck,, G. Bagby,, M. Finegold,, S. Olson, and, M. Grompe. 2002. Fanconi anemia group A and C double–mutant mice: functional evidence for a multi–protein Fanconi anemia complex. Exp. Hematol. 30:679688.
118. Nystrom–Lahti, M.,, P. Sistonen,, J. P. Mecklin,, L. Pylkkanen,, L. A. Aaltonen,, H. Jarvinen,, J. Weissenbach,, A. de la Chapelle, and, P. Peltomaki. 1994. Close linkage to chromosome 3p and conservation of ancestral founding haplotype in hereditary nonpolyposis colorectal cancer families. Proc. Natl. Acad. Sci. USA 91:60546058.
119. Ohmiya, N.,, S. Matsumoto,, H. Yamamoto,, S. Baranovskaya,, S. R. Malkhosyan, and, M. Perucho. 2001. Germline and somatic mutations in hMSH6 and hMSH3 in gastrointestinal cancers of the microsatellite mutator phenotype. Gene 272:301313.
120. Pagano, G., and, H. Youssoufian. 2003. Fanconi anaemia proteins: major roles in cell protection against oxidative damage. Bioessays 25:589595.
121. Pang, Q.,, T. A. Christianson,, W. Keeble,, J. Diaz,, G. R. Faulkner,, C. Reifsteck,, S. Olson, and, G. C. Bagby. 2001. The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality. Blood 98:13921401.
122. Pang, Q.,, S. Fagerlie,, T. A. Christianson,, W. Keeble,, G. Faulkner,, J. Diaz,, R. K. Rathbun, and, G. C. Bagby. 2000. The Fanconi anemia protein FANCC binds to and facilitates the activation of STAT1 by gamma interferon and hematopoietic growth factors. Mol. Cell. Biol. 20:47244735.
123. Papadopoulo, D.,, D. Averbeck, and, E. Moustacchi. 1987. The fate of 8–methoxypsoralen–photoinduced DNA interstrand crosslinks in Fanconi’s anemia cells of defined genetic complementation groups. Mutat. Res. 184:271280.
124. Papadopoulo, D.,, C. Guillouf,, H. Mohrenweiser, and, E. Moustacchi. 1990. Hypomutability in Fanconi anemia cells is associated with increased deletion frequency at the HPRT locus. Proc. Natl. Acad. Sci. USA 87:83838387.
125. Papadopoulo, D.,, B. Porfirio, and, E. Moustacchi. 1990. Mutagenic response of Fanconi’s anemia cells from a defined complementation group after treatment with photoactivated bifunctional psoralens. Cancer Res. 50:32893294.
126. Papadopoulos, N.,, N. C. Nicolaides,, Y. F. Wei,, S. M. Ruben,, K. C. Carter,, C. A. Rosen,, W. A. Haseltine,, R. D. Fleischmann,, C. M. Fraser,, M. D. Adams,, J. C. Venter,, S. R. Hamilton,, G. M. Petersen,, P. Watson,, H. T. Lynch,, P. Peltomaki,, J. P. Mecklin,, A. Delachapelle,, K. W. Kinzler, and, B. Vogelstein. 1994. Mutation of a mutL homolog in hereditary colon cancer. Science 263:16251629.
127. Parc, Y. R.,, K. C. Halling,, L. Wang,, E. R. Christensen,, J. M. Cunningham,, A. J. French,, L. J. Burgart,, T. L. Price–Troska,, P. C. Roche, and, S. N. Thibodeau. 2000. HMSH6 alterations in patients with microsatellite instability–low colorectal cancer. Cancer Res. 60:22252231.
128. Parsons, R.,, G. M. Li,, M. J. Longley,, W. H. Fang,, N. Papadopoulos,, J. Jen,, A. de la Chapelle,, K. W. Kinzler,, B. Vogelstein, and, P. Modrich. 1993. Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell 75:12271236.
129. Peltomaki, P., 2003. Role of DNA mismatch repair defects in the pathogenesis of human cancer. J. Clin. Oncol. 21:11741179.
130. Peltomaki, P.,, L. A. Aaltonen,, P. Sistonen,, L. Pylkkanen,, J. P. Mecklin,, H. Jarvinen,, J. S. Green,, J. R. Jass,, J. L. Weber,, F. S. Leach,, G. M. Petersen,, S. R. Hamilton,, A. Delachapelle, and, B. Vogelstein. 1993. Genetic mapping of a locus predisposing to human colorectal cancer. Science 260:810812.
131. Peltomaki, P., and, A. de la Chapelle. 1997. Mutations predisposing to hereditary nonpolyposis colorectal cancer. Adv. Cancer Res. 71:93119.
132. Poll, E. H.,, F. Arwert,, H. T. Kortbeek, and, A. W. Eriksson. 1984. Fanconi anaemia cells are not uniformly deficient in unhooking of DNA interstrand crosslinks, induced by mitomycin C or 8–methoxypsoralen plus UVA. Hum. Genet. 68:228234.
133. Prolla, T. A.,, S. M. Baker,, A. C. Harris,, J. L. Tsao,, X. Yao,, C. E. Bronner,, B. Zheng,, M. Gordon,, J. Reneker,, N. Arnheim,, D. Shibata,, A. Bradley, and, R. M. Liskay. 1998. Tumour susceptibility and spontaneous mutation in mice deficient in Mlh1, Pms1 and Pms2 DNA mismatch repair. Nat. Genet. 18:276279.
134. Purandare, S. M., and, P. I. Patel. 1997. Recombination hot spots and human disease. Genome Res. 7:773786.
135. Rathbun, R. K.,, T. A. Christianson,, G. R. Faulkner,, G. Jones,, W. Keeble,, M. O’Dwyer, and, G. C. Bagby. 2000. Interferon–gamma–induced apoptotic responses of Fanconi anemia group C hematopoietic progenitor cells involve caspase 8–dependent activation of caspase 3 family members. Blood 96:42044211.
136. Rathbun, R. K.,, G. R. Faulkner,, M. H. Ostroski,, T. A. Christianson,, G. Hughes,, G. Jones,, R. Cahn,, R. Maziarz,, G. Royle,, W. Keeble,, M. C. Heinrich,, M. Grompe,, P. A. Tower, and, G. C. Bagby. 1997. Inactivation of the Fanconi anemia group C gene augments interferon–gamma–induced apoptotic responses in hematopoietic cells. Blood 90:974985.
137. Reinhold, J. D.,, E. Neumark,, R. Lightwood, and, C. O. Carter. 1952. Familial hypoplastic anemia with congenital abnormalities (Fanconi’s syndrome). Blood 7:915926.
138. Reitmair, A. H.,, R. Schmits,, A. Ewel,, B. Bapat,, M. Redston,, A. Mitri,, P. Waterhouse,, H. W. Mittrucker,, A. Wakeham,, B. Liu,, A. Thomason,, H. Griesser,, S. Gallinger,, W. G. Ballhausen,, R. Fishel, and, T. W. Mak. 1995. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat. Genet. 11:6470.
139. Ricciardone, M. D.,, T. Ozcelik,, B. Cevher,, H. Ozdag,, M. Tuncer,, A. Gurgey,, O. Uzunalimoglu,, H. Cetinkaya,, A. Tanyeli,, E. Erken, and, M. Ozturk. 1999. Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1. Cancer Res. 59:290293.
140. Rio, P.,, J. C. Segovia,, H. Hanenberg,, J. A. Casado,, J. Martinez,, K. Gottsche,, N. C. Cheng,, H. J. Van de Vrugt,, F. Arwert,, H. Joenje, and, J. A. Bueren. 2002. In vitro phenotypic correction of hematopoietic progenitors from Fanconi anemia group A knockout mice. Blood 100:20322039.
141. Rosselli, F.,, A. Ridet,, T. Soussi,, E. Duchaud,, C. Alapetite, and, E. Moustacchi. 1995. p53–dependent pathway of radio–induced apoptosis is altered in Fanconi anemia. Oncogene 10:917.
142. Rosselli, F.,, J. Sanceau,, J. Wietzerbin, and, E. Moustacchi. 1992. Abnormal lymphokine production: a novel feature of the genetic disease Fanconi anemia. I. Involvement of interleukin–6. Hum. Genet. 89:4248.
143. Rousset, S.,, S. Nocentini,, B. Revet, and, E. Moustacchi. 1990. Molecular analysis by electron microscopy of the removal of psoralen–photoinduced DNA cross–links in normal and Fanconi’s anemia fibro– blasts. Cancer Res. 50:24432448.
144. Saar, K.,, D. Schindler,, R. D. Wegner,, A. Reis,, T. F. Wienker,, H. Hoehn,, H. Joenje,, K. Sperling, and, M. Digweed. 1998. Localisation of a Fanconi anaemia gene to chromosome 9p. Eur. J. Hum. Genet. 6:501508.
145. Saito, H.,, A. T. Hammond, and, R. E. Moses. 1993. Hypersensitivity to oxygen is a uniform and secondary defect in Fanconi anemia cells. Mutat. Res. 294:255262.
146. Sakaguchi, K.,, P. V. Harris,, C. Ryan,, M. Buchwald, and, J. B. Boyd. 1991. Alteration of a nuclease in Fanconi anemia. Mutat. Res. 255:3138..
147. Sasaki, M. S., and, A. Tonomura. 1973. A high susceptibility of Fanconi’s anemia to chromosome breakage by DNA cross–linking agents. Cancer Res. 33:18291836.
148. Savino, M.,, L. Ianzano,, P. Strippoli,, U. Ramenghi,, A. Arslanian,, G. P. Bagnara,, H. Joenje,, L. Zelante, and, A. Savoia. 1997. Mutations of the Fanconi anemia group A gene (FAA) in Italian patients. Am. J. Hum. Genet. 61:12461253.
149. Schroeder, T. M., and, R. Kurth. 1971. Spontaneous chromosomal breakage and high incidence of leukemia in inherited disease. Blood 37:96112.
150. Schroeder, T. M.,, D. Tilgen,, J. Kruger, and, F. Vogel. 1976. Formal genetics of Fanconi’s anemia. Hum. Genet. 32:257288.
151. Schultz, J. C., and, N. T. Shahidi. 1993. Tumor necrosis factor–alpha overproduction in Fanconi’s anemia. Am. J. Hematol. 42:196201.
152. Smits, R.,, N. Holland,, W. Edelmann,, M. Geugien,, S. Jagmohan–Changur,, C. Albuquerque,, C. Breukel,, R. Kucherlapati,, M. F. Kielman, and, R. Fodde. 2000. Somatic Apc mutations are selected upon their capacity to inactivate the beta–catenin downregulating activity. Genes Chromosomes Cancer 29:229239.
153. Strand, M.,, T. A. Prolla,, R. M. Liskay, and, T. D. Petes. 1993. Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365:274276.
154. Strathdee, C. A.,, A. M. Duncan, and, M. Buchwald. 1992. Evidence for at least four Fanconi anaemia genes including FACC on chromosome 9. Nat. Genet. 1:196198.
155. Strathdee, C. A.,, H. Gavish,, W. R. Shannon, and, M. Buchwald. 1992. Cloning of cDNAs for Fanconi’s anaemia by functional complementation. Nature 358:434.
156. Streisinger, G.,, Y. Okada,, J. Emrich,, J. Newton,, A. Tsugita,, E. Terzaghi, and, M. Inouye. 1966. Frameshift mutations and the genetic code. This paper is dedicated to Professor Theodosius Dobzhansky on the occasion of his 66th birthday. Cold Spring Harbor Symp. Quant. Biol. 31: 7784.
157. Swift, M.,, D. Zimmerman, and, E. R. McDonough. 1971. Squamous cell carcinomas in Fanconi’s anemia. JAMA 216:325326.
158. Swift, M. R., and, K. Hirschhorn. 1966. Fanconi’s anemia. Inherited susceptibility to chromosome breakage in various tissues. Ann. Intern. Med. 65:496503.
159. Takeuchi, T., and, K. Morimoto. 1993. Increased formation of 8–hydroxydeoxyguanosine, an oxidative DNA damage, in lymphoblasts from Fanconi’s anemia patients due to possible catalase deficiency. Carcinogenesis 14:11151120.
160. Taniguchi, T., and, A. D. D’Andrea. 2002. The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC. Blood 100:24572462.
161. Thibodeau, S. N.,, G. Bren, and, D. Schaid. 1993. Microsatellite instability in cancer of the proximal colon. Science 260:816819.
162. Timmers, C.,, T. Taniguchi,, J. Hejna,, C. Reifsteck,, L. Lucas,, D. Bruun,, M. Thayer,, B. Cox,, S. Olson,, A. D. D’Andrea,, R. Moses, and, M. Grompe. 2001. Positional cloning of a novel Fanconi anemia gene, FANCD2. Mol. Cell 7:241248.
163. Tipping, A. J.,, T. Pearson,, N. V. Morgan,, R. A. Gibson,, L. P. Kuyt,, C. Havenga,, E. Gluckman,, H. Joenje,, T. de Ravel,, S. Jansen, and, C. G. Mathew. 2001. Molecular and genealogical evidence for a founder effect in Fanconi anemia families of the Afrikaner population of South Africa. Proc. Natl. Acad. Sci. USA 98:57345739.
164. Tischkowitz, M., and, I. Dokal. 2004. Fanconi anaemia and leukaemia: clinical and molecular aspects. Br. J. Haematol. 126:176191.
165. Tomizawa, J., and, T. Som. 1984. Control of ColE1 plasmid replication: enhancement of binding of RNA I to the primer transcript by the Rom protein. Cell 38:871878.
166. Tutt, A.,, D. Bertwistle,, J. Valentine,, A. Gabriel,, S. Swift,, G. Ross,, C. Griffin,, J. Thacker, and, A. Ashworth. 2001. Mutation in Brca2 stimulates error–prone homology–directed repair of DNA double–strand breaks occurring between repeated sequences. EMBO J. 20:47044716.
167. Vasen, H. F.,, J. P. Mecklin,, P. M. Khan, and, H. T. Lynch. 1991. The International Collaborative Group on Hereditary Non–Polyposis Colorectal Cancer (ICG–HNPCC). Dis. Colon Rectum 34:42425.
168. Vasen, H. F.,, P. Watson,, J. P. Mecklin, and, H. T. Lynch. 1999. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116:14531456.
169. Vasen, H. F.,, J. T. Wijnen,, F. H. Menko,, J. H. Kleibeuker,, B. G. Taal,, G. Griffioen,, F. M. Nagengast,, E. H. Meijers–Heijboer,, L. Bertario,, L. Varesco,, M. L. Bisgaard,, J. Mohr,, R. Fodde, and, P. M. Khan. 1996. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 110:10201027.
170. Verlander, P. C.,, A. Kaporis,, Q. Liu,, Q. Zhang,, U. Seligsohn, and, A. D. Auerbach. 1995. Carrier frequency of the IVS4 + 4 A → T mutation of the Fanconi anemia gene FAC in the Ashkenazi Jewish population. Blood 86:40344038.
171. Verma, L.,, M. F. Kane,, C. Brassett,, J. Schmeits,, D. G. Evans,, R. D. Kolodner, and, E. R. Maher. 1999. Mononucleotide microsatellite instability and germline MSH6 mutation analysis in early onset colorectal cancer. J. Med. Genet. 36:678682.
172. Waisfisz, Q.,, K. Saar,, N. V. Morgan,, C. Altay,, P. A. Leegwater,, J. P. de Winter,, K. Komatsu,, G. R. Evans,, R. D. Wegner,, A. Reis,, H. Joenje,, F. Arwert,, C. G. Mathew,, J. C. Pronk, and, M. Digweed. 1999. The Fanconi anemia group E gene, FANCE, maps to chromosome 6p. Am. J. Hum. Genet. 64:14001405.
173. Wang, Q.,, C. Lasset,, F. Desseigne,, D. Frappaz,, C. Bergeron,, C. Navarro,, E. Ruano, and, A. Puisieux. 1999. Neurofibromatosis and early onset of cancers in hMLH1–deficient children. Cancer Res. 59:294297.
174. Wang, X., and, A. D. D’Andrea. 2004. The interplay of Fanconi anemia proteins in the DNA damage response. DNA Repair 3:10631069.
175. Wei, K.,, R. Kucherlapati, and, W. Edelmann. 2002. Mouse models for human DNA mismatch–repair gene defects. Trends Mol. Med. 8:346353.
176. Whitney, M.,, M. Thayer,, C. Reifsteck,, S. Olson,, L. Smith,, P. M. Jakobs,, R. Leach,, S. Naylor,, H. Joenje, and, M. Grompe. 1995. Microcell mediated chromosome transfer maps the Fanconi anaemia group D gene to chromosome 3p. Nat. Genet. 11:341343.
177. Whitney, M. A.,, P. Jakobs,, M. Kaback,, R. E. Moses, and, M. Grompe. 1994. The Ashkenazi Jewish Fanconi anemia mutation: incidence among patients and carrier frequency in the at–risk population. Hum. Mutat. 3:339341.
178. Whitney, M. A.,, G. Royle,, M. J. Low,, M. A. Kelly,, M. K. Axthelm,, C. Reifsteck,, S. Olson,, R. E. Braun,, M. C. Heinrich,, R. K. Rath–bun,, G. C. Bagby, and, M. Grompe. 1996. Germ cell defects and hematopoietic hypersensitivity to gamma–interferon in mice with a targeted disruption of the Fanconi anemia C gene. Blood 88:4958.
179. Whitney, M. A.,, H. Saito,, P. M. Jakobs,, R. A. Gibson,, R. E. Moses, and, M. Grompe. 1993. A common mutation in the FACC gene causes Fanconi anaemia in Ashkenazi Jews. Nat. Genet. 4:202205.
180. Wijker, M.,, N. V. Morgan,, S. Herterich,, C. G. van Berkel,, A. J. Tipping,, H. J. Gross,, J. J. Gille,, G. Pals,, M. Savino,, C. Altay,, S. Mohan,, I. Dokal,, J. Cavenagh,, J. Marsh,, M. van Weel,, J. J. Ortega,, D. Schuler,, E. Samochatova,, M. Karwacki,, A. N. Bekassy, et al., 1999. Heterogeneous spectrum of mutations in the Fanconi anaemia group A gene. Eur. J. Hum. Genet. 7:5259.
181. Wijnen, J.,, W. de Leeuw,, H. Vasen,, H. van der Klift,, P. Moller,, A. Stormorken,, H. Meijers–Heijboer,, D. Lindhout,, F. Menko,, S. Vossen,, G. Moslein,, C. Tops,, A. Brocker–Vriends,, Y. Wu,, R. Hofstra,, R. Sijmons,, C. Cornelisse,, H. Morreau, and, R. Fodde. 1999. Familial endometrial cancer in female carriers of MSH6 germline mutations. Nat. Genet. 23:142144.
182. Wong, J. C., and, M. Buchwald. 2002. Disease model: Fanconi anemia. Trends Mol. Med. 8:139142.
183. Wu, Y.,, M. J. Berends,, J. G. Post,, R. G. Mensink,, E. Verlind,, T. Van Der Sluis,, C. Kempinga,, R. H. Sijmons,, A. G. van der Zee,, H. Hollema,, J. H. Kleibeuker,, C. H. Buys, and, R. M. Hofstra. 2001. Germline mutations of EXO1 gene in patients with hereditary nonpolyposis colorectal cancer (HNPCC) and atypical HNPCC forms. Gastroenterology 120:15801587.
184. Wu, Y.,, M. J. Berends,, R. H. Sijmons,, R. G. Mensink,, E. Verlind,, K. A. Kooi,, T. van der Sluis,, C. Kempinga,, A. G. van der Zee,, H. Hollema,, C. H. Buys,, J. H. Kleibeuker, and, R. M. Hofstra. 2001. A role for MLH3 in hereditary nonpolyposis colorectal cancer. Nat. Genet. 29:137138.
185. Wunder, E.,, B. T. Mortensen,, F. Schilling, and, P. R. Henon. 1993. Anomalous plasma concentrations and impaired secretion of growth factors in Fanconi’s anemia. Stem Cells 11(Suppl., 2):144149.
186. Yamashita, T.,, D. L. Barber,, Y. Zhu,, N. Wu, and, A. D. D’Andrea. 1994. The Fanconi anemia polypeptide FACC is localized to the cytoplasm. Proc. Natl. Acad. Sci. USA 91:67126716.
187. Yamashita, T.,, G. M. Kupfer,, D. Naf,, A. Suliman,, H. Joenje,, S. Asano, and, A. D. D’Andrea. 1998. The Fanconi anemia pathway requires FAA phosphorylation and FAA/FAC nuclear accumulation. Proc. Natl. Acad. Sci. USA 95:1308513090.
188. Yang, Y.,, Y. Kuang,, R. M. De Oca,, T. Hays,, L. Moreau,, N. Lu,, B. Seed, and, A. D. D’Andrea. 2001. Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9. Blood 98:34353440.
189. Yao, X.,, A. B. Buermeyer,, L. Narayanan,, D. Tran,, S. M. Baker,, T. A. Prolla,, P. M. Glazer,, R. M. Liskay, and, N. Arnheim. 1999. Different mutator phenotypes in Mlh1– versus Pms2–deficient mice. Proc. Natl. Acad. Sci. USA 96:68506855.
190. Yin, J.,, D. Kong,, S. Wang,, T. T. Zou,, R. F. Souza,, K. N. Smolinski,, P. M. Lynch,, S. R. Hamilton,, H. Sugimura,, S. M. Powell,, J. Young,, J. M. Abraham, and, S. J. Meltzer. 1997. Mutation of hMSH3 and hMSH6 mismatch repair genes in genetically unstable human colorectal and gastric carcinomas. Hum. Mutat. 10:474478.
191. Young, N. S., and, B. P. Alter. 1993. Aplastic Anemia—Acquired and Inherited. The W. B. Saunders Co., Philadelphia, Pa.
192. Youssoufian, H., 1994. Localization of Fanconi anemia C protein to the cytoplasm of mammalian cells. Proc. Natl. Acad. Sci. USA 91:79757979.
193. Zhen, W.,, M. K. Evans,, C. M. Haggerty, and, V. A. Bohr. 1993. Deficient gene specific repair of cisplatin–induced lesions in xeroderma pigmentosum and Fanconi’s anemia cell lines. Carcinogenesis 14:919924.