DNA instability at chromosomal fragile sites in cancer

Current Genomics

Volumn 11, Issue 5, 2010, Pages 326-337

  Dillon, Laura W ^a   Burrow, Allison A ^a   Wang, Yuh Hwa ^a  

^a WAKE FOREST SCHOOL OF MEDICINE   (United States)

Author keywords

ATR checkpoint pathway; Cancer specific chromosomal translocation; DNA secondary structure; Environmental mutagen; Fragile site; RET PTC rearrangement; Stalled replication fork

Indexed keywords

ALCOHOL; ATENOLOL; ATM PROTEIN; ATR PROTEIN; AZACITIDINE; BENZENE; BLEOMYCIN; BRCA1 PROTEIN; BROXURIDINE; BUSULFAN; CAFFEINE; CARBON TETRACHLORIDE; CHLORAMBUCIL; CIGARETTE SMOKE; CYTARABINE; DACTINOMYCIN; DIETHYLNITROSAMINE; DIMETHYL SULFATE; DIMINAZENE ACETURATE; DISTAMYCIN A; DNA POLYMERASE; FANCONI ANEMIA GROUP D2 PROTEIN; FLOXURIDINE; FRAGILE HISTIDINE TRIAD PROTEIN; METHOTREXATE; PESTICIDE; PROTEIN PATCHED 1; WERNER SYNDROME PROTEIN;

ALLELE; ARTICLE; CANCER GENETICS; CANCER GROWTH; CARCINOGENESIS; CHROMOSOMAL INSTABILITY; CHROMOSOME ABERRATION; CHROMOSOME FRAGILE SITE; CHROMOSOME FRAGILITY; CHROMOSOME REARRANGEMENT; CHROMOSOME REPLICATION; DNA DAMAGE; DNA REPLICATION; DNA STRAND BREAKAGE; GENE DELETION; GENE EXPRESSION; GENE TRANSLOCATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; HUMAN; HYPOXIA; METAPHASE CHROMOSOME; NONHUMAN; REACTION ANALYSIS; THYROID CARCINOMA; TUMOR SUPPRESSOR GENE;

EID: 77956539396     PISSN: 13892029     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920210791616699     Document Type: Article

References (113)

1. Jackson, S. P. Sensing and repairing DNA double-strand breaks. Carcinogenesis, 2002, 23, 687-96.
2. O'Keefe, L. V.; Richards, R. I. Common chromosomal fragile sites and cancer: focus on FRA16D. Cancer Lett., 2006, 232, 37-47.
3. Richards, R. I. Fragile and unstable chromosomes in cancer: causes and consequences. Trends Genet., 2001, 17, 339-345.
4. Popescu, N. C. Genetic alterations in cancer as a result of breakage at fragile sites. Cancer Lett., 2003, 192, 1-17.
5. Yunis, J. J.; Soreng, A. L. Constitutive fragile sites and cancer. Science, 1984, 226, 1199-1204.
6. Durkin, S. G.; Glover, T. W. Chromosome fragile sites. Annu. Rev. Genet., 2007, 41, 169-192.
7. Re, A.; Cora, D.; Puliti, A. M.; Caselle, M.; Sbrana, I. Correlated fragile site expression allows the identification of candidate fragile genes involved in immunity and associated with carcinogenesis. BMC Bioinformatics, 2006, 7, 413.
8. Gandhi, M.; Dillon, L. W.; Pramanik, S.; Nikiforov, Y. E.; Wang, Y. H. DNA breaks at fragile sites generate oncogenic RET/PTC rearrangements in human thyroid cells. Oncogene, 2010, 29, 2270-2280.
9. Glover, T. W. Common fragile sites. Cancer Lett., 2006, 232, 4-12.
10. Glover, T. W.; Berger, C.; Coyle, J.; Echo, B. DNA polymerase alpha inhibition by aphidicolin induces gaps and breaks at common fragile sites in human chromosomes. Hum. Genet., 1984, 67, 136-142.
11. Cheng, C. H.; Kuchta, R. D. DNA polymerase epsilon: aphidicolin inhibition and the relationship between polymerase and exonuclease activity. Biochemistry, 1993, 32, 8568-8574.
12. Kremer, E. J.; Pritchard, M.; Lynch, M.; Yu, S.; Holman, K.; Baker, E.; Warren, S. T.; Schlessinger, D.; Sutherland, G. R.; Richards, R. I. Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. Science, 1991, 252, 1711-1714.
13. Sutherland, G. R.; Baker, E.; Richards, R. I. Fragile sites still breaking. Trends Genet., 1998, 14, 501-506.
14. Mrasek, K.; Schoder, C.; Teichmann, A. C.; Behr, K.; Franze, B.; Wilhelm, K.; Blaurock, N.; Claussen, U.; Liehr, T.; Weise, A. Global screening and extended nomenclature for 230 aphidicolininducible fragile sites, including 61 yet unreported ones. Int. J. Oncol., 2010, 36, 929-940.
15. Mishmar, D.; Rahat, A.; Scherer, S. W.; Nyakatura, G.; Hinzmann, B.; Kohwi, Y.; Mandel-Gutfroind, Y.; Lee, J. R.; Drescher, B.; Sas, D. E.; Margalit, H.; Platzer, M.; Weiss, A.; Tsui, L. C.; Rosenthal, A.; Kerem, B. Molecular characterization of a common fragile site (FRA7H) on human chromosome 7 by the cloning of a simian virus 40 integration site. Proc. Natl. Acad. Sci. USA, 1998, 95, 8141-8146.
16. Zlotorynski, E.; Rahat, A.; Skaug, J.; Ben-Porat, N.; Ozeri, E.; Hershberg, R.; Levi, A.; Scherer, S. W.; Margalit, H.; Kerem, B. Molecular basis for expression of common and rare fragile sites. Mol. Cell. Biol., 2003, 23, 7143-7151.
17. McAvoy, S.; Ganapathiraju, S. C.; Ducharme-Smith, A. L.; Pritchett, J. R.; Kosari, F.; Perez, D. S.; Zhu, Y.; James, C. D.; Smith, D. I. Non-random inactivation of large common fragile site genes in different cancers. Cytogenet. Genome Res., 2007, 118, 260-269.
18. Hansen, R. S.; Canfield, T. K.; Fjeld, A. D.; Mumm, S.; Laird, C. D.; Gartler, S. M. A variable domain of delayed replication in FRAXA fragile X chromosomes: X inactivation-like spread of late replication. Proc. Natl. Acad. Sci. USA, 1997, 94, 4587-4592.
19. Le Beau, M. M.; Rassool, F. V.; Neilly, M. E.; Espinosa, R., 3rd; Glover, T. W.; Smith, D. I.; McKeithan, T. W. Replication of a common fragile site, FRA3B, occurs late in S phase and is delayed further upon induction: implications for the mechanism of fragile site induction. Hum. Mol. Genet., 1998, 7, 755-761.
20. Hellman, A.; Rahat, A.; Scherer, S. W.; Darvasi, A.; Tsui, L. C.; Kerem, B. Replication delay along FRA7H, a common fragile site on human chromosome 7, leads to chromosomal instability. Mol. Cell. Biol., 2000, 20, 4420-4427.
21. Handt, O.; Baker, E.; Dayan, S.; Gartler, S. M.; Woollatt, E.; Richards, R. I.; Hansen, R. S. Analysis of replication timing at the FRA10B and FRA16B fragile site loci. Chromosome Res., 2000, 8, 677-688.
22. Pelliccia, F.; Bosco, N.; Curatolo, A.; Rocchi, A. Replication timing of two human common fragile sites: FRA1H and FRA2G. Cytogenet. Genome Res., 2008, 121, 196-200.
23. Casper, A. M.; Nghiem, P.; Arlt, M. F.; Glover, T. W. ATR regulates fragile site stability. Cell, 2002, 111, 779-789.
24. Casper, A. M.; Durkin, S. G.; Arlt, M. F.; Glover, T. W. Chromosomal instability at common fragile sites in Seckel syndrome. Am. J. Hum. Genet., 2004, 75, 654-660.
25. Arlt, M. F.; Xu, B.; Durkin, S. G.; Casper, A. M.; Kastan, M. B.; Glover, T. W. BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function. Mol. Cell. Biol., 2004, 24, 6701-6709.
26. Durkin, S. G.; Arlt, M. F.; Howlett, N. G.; Glover, T. W. Depletion of CHK1, but not CHK2, induces chromosomal instability and breaks at common fragile sites. Oncogene, 2006, 25, 4381-4388.
27. Glover, T. W.; Stein, C. K. Induction of sister chromatid exchanges at common fragile sites. Am. J. Hum. Genet., 1987, 41, 882-890.
28. Glover, T. W.; Stein, C. K. Chromosome breakage and recombination at fragile sites. Am. J. Hum. Genet., 1988, 43, 265-273.
29. Glover, T. W.; Coyle-Morris, J.; Morgan, R. Fragile sites: overview, occurrence in acute nonlymphocytic leukemia and effects of caffeine on expression. Cancer Genet. Cytogenet., 1986, 19, 141-150.
30. Kuwano, A.; Kajii, T. Synergistic effect of aphidicolin and ethanol on the induction of common fragile sites. Hum. Genet., 1987, 75, 75-78.
31. Demirhan, O.; Tastemir, D. Cytogenetic effects of ethanol on chronic alcohol users. Alcohol Alcohol, 2008, 43, 127-136.
32. Coquelle, A.; Toledo, F.; Stern, S.; Bieth, A.; Debatisse, M. A new role for hypoxia in tumor progression: induction of fragile site triggering genomic rearrangements and formation of complex DMs and HSRs. Mol. Cell, 1998, 2, 259-265.
33. Kao-Shan, C. S.; Fine, R. L.; Whang-Peng, J.; Lee, E. C.; Chabner, B. A. Increased fragile sites and sister chromatid exchanges in bone marrow and peripheral blood of young cigarette smokers. Cancer Res., 1987, 47, 6278-6282.
34. Stein, C. K.; Glover, T. W.; Palmer, J. L.; Glisson, B. S. Direct correlation between FRA3B expression and cigarette smoking. Genes Chromosomes Cancer, 2002, 34, 333-340.
35. Musio, A.; Sbrana, I. Aphidicolin-sensitive specific common fragile sites: a biomarker of exposure to pesticides. Environ. Mol. Mutagen., 1997, 29, 250-255.
36. Sbrana, I.; Musio, A. Enhanced expression of common fragile site with occupational exposure to pesticides. Cancer Genet. Cytogenet., 1995, 82, 123-127.
37. Blair, A.; Zahm, S. H. Cancer among farmers. Occup. Med., 1991, 6, 335-354.
38. Brown, L. M.; Blair, A.; Gibson, R.; Everett, G. D.; Cantor, K. P.; Schuman, L. M.; Burmeister, L. F.; Van Lier, S. F.; Dick, F. Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and Minnesota. Cancer Res., 1990, 50, 6585-6591.
39. Webster, L. R.; McKenzie, G. H.; Moriarty, H. T. Organophosphate-based pesticides and genetic damage implicated in bladder cancer. Cancer Genet. Cytogenet., 2002, 133, 112-117.
40. Yunis, J. J.; Soreng, A. L.; Bowe, A. E. Fragile sites are targets of diverse mutagens and carcinogens. Oncogene, 1987, 1, 59-69.
41. Telez, M.; Ortiz-Lastra, E.; Gonzalez, A. J.; Flores, P.; Huerta, I.; Ramirez, J. M.; Barasoain, M.; Criado, B.; Arrieta, I. Assessment of the genotoxicity of atenolol in human peripheral blood lymphocytes: correlation between chromosomal fragility and content of micronuclei. Mutat. Res., 2010, 695, 46-54.
42. Brambilla, G.; Martelli, A. Genotoxicity and carcinogenicity studies of antihypertensive agents. Mutat. Res., 2006, 612, 115-149.
43. Telez, M.; Martinez, B.; Criado, B.; Lostao, C. M.; Penagarikano, O.; Ortega, B.; Flores, P.; Ortiz-Lastra, E.; Alonso, R. M.; Jimenez, R. M.; Arrieta, I. In vitro and in vivo evaluation of the antihypertensive drug atenolol in cultured human lymphocytes: effects of long-term therapy. Mutagenesis, 2000, 15, 195-202.
44. Craig-Holmes, A. P.; Strong, L. C.; Goodacre, A.; Pathak, S. Variation in the expression of aphidicolin-induced fragile sites in human lymphocyte cultures. Hum. Genet., 1987, 76, 134-137.
45. Tunca, B.; Egeli, U.; Zorluoglu, A.; Yilmazlar, T.; Yerci, O.; Kizil, A. The expression of fragile sites in lymphocytes of patients with rectum cancer and their first-degree relatives. Cancer Lett., 2000, 152, 201-209.
46. Kameoka, Y.; Tagawa, H.; Tsuzuki, S.; Karnan, S.; Ota, A.; Suguro, M.; Suzuki, R.; Yamaguchi, M.; Morishima, Y.; Nakamura, S.; Seto, M. Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma. Oncogene, 2004, 23, 9148-9154.
47. Lee, S. H.; Kim, W. H.; Kim, H. K.; Woo, K. M.; Nam, H. S.; Kim, H. S.; Kim, J. G.; Cho, M. H. Altered expression of the fragile histidine triad gene in primary gastric adenocarcinomas. Biochem. Biophys. Res. Commun., 2001, 284, 850-855.
48. Michael, D.; Beer, D. G.; Wilke, C. W.; Miller, D. E.; Glover, T. W. Frequent deletions of FHIT and FRA3B in Barrett's metaplasia and esophageal adenocarcinomas. Oncogene, 1997, 15, 1653-1659.
49. Sozzi, G.; Veronese, M. L.; Negrini, M.; Baffa, R.; Cotticelli, M. G.; Inoue, H.; Tornielli, S.; Pilotti, S.; De Gregorio, L.; Pastorino, U.; Pierotti, M. A.; Ohta, M.; Huebner, K.; Croce, C. M. The FHIT gene 3p14.2 is abnormal in lung cancer. Cell, 1996, 85, 17-26.
50. Virgilio, L.; Shuster, M.; Gollin, S. M.; Veronese, M. L.; Ohta, M.; Huebner, K.; Croce, C. M. FHIT gene alterations in head and neck squamous cell carcinomas. Proc. Natl. Acad. Sci. USA, 1996, 93, 9770-9775.
51. Huebner, K.; Croce, C. M. FRA3B and other common fragile sites: the weakest links. Nat. Rev. Cancer, 2001, 1, 214-221.
52. Driouch, K.; Prydz, H.; Monese, R.; Johansen, H.; Lidereau, R.; Frengen, E. Alternative transcripts of the candidate tumor suppressor gene, WWOX, are expressed at high levels in human breast tumors. Oncogene, 2002, 21, 1832-1840.
53. Kuroki, T.; Trapasso, F.; Shiraishi, T.; Alder, H.; Mimori, K.; Mori, M.; Croce, C. M. Genetic alterations of the tumor suppressor gene WWOX in esophageal squamous cell carcinoma. Cancer Res., 2002, 62, 2258-2260.
54. Kuroki, T.; Yendamuri, S.; Trapasso, F.; Matsuyama, A.; Aqeilan, R. I.; Alder, H.; Rattan, S.; Cesari, R.; Nolli, M. L.; Williams, N. N.; Mori, M.; Kanematsu, T.; Croce, C. M. The tumor suppressor gene WWOX at FRA16D is involved in pancreatic carcinogenesis. Clin. Cancer Res., 2004, 10, 2459-2465.
55. Paige, A. J.; Taylor, K. J.; Taylor, C.; Hillier, S. G.; Farrington, S.; Scott, D.; Porteous, D. J.; Smyth, J. F.; Gabra, H.; Watson, J. E. WWOX: a candidate tumor suppressor gene involved in multiple tumor types. Proc. Natl. Acad. Sci. USA, 2001, 98, 11417-11422.
56. Ried, K.; Finnis, M.; Hobson, L.; Mangelsdorf, M.; Dayan, S.; Nancarrow, J. K.; Woollatt, E.; Kremmidiotis, G.; Gardner, A.; Venter, D.; Baker, E.; Richards, R. I. Common chromosomal fragile site FRA16D sequence: identification of the FOR gene spanning FRA16D and homozygous deletions and translocation breakpoints in cancer cells. Hum. Mol. Genet., 2000, 9, 1651-1663.
57. Yendamuri, S.; Kuroki, T.; Trapasso, F.; Henry, A. C.; Dumon, K. R.; Huebner, K.; Williams, N. N.; Kaiser, L. R.; Croce, C. M. WW domain containing oxidoreductase gene expression is altered in non-small cell lung cancer. Cancer Res., 2003, 63, 878-881.
58. McClintock, B. Chromosome organization and genic expression. Cold Spring Harb. Symp. Quant. Biol., 1951, 16, 13-47.
59. Coquelle, A.; Pipiras, E.; Toledo, F.; Buttin, G.; Debatisse, M. Expression of fragile sites triggers intrachromosomal mammalian gene amplification and sets boundaries to early amplicons. Cell, 1997, 89, 215-225.
60. Zimonjic, D. B.; Keck-Waggoner, C. L.; Yuan, B. Z.; Kraus, M. H.; Popescu, N. C. Profile of genetic alterations and tumorigenicity of human breast cancer cells. Int. J. Oncol., 2000, 16, 221-230.
61. Hellman, A.; Zlotorynski, E.; Scherer, S. W.; Cheung, J.; Vincent, J. B.; Smith, D. I.; Trakhtenbrot, L.; Kerem, B. A role for common fragile site induction in amplification of human oncogenes. Cancer Cell, 2002, 1, 89-97.
62. Popescu, N. C.; DiPaolo, J. A.; Amsbaugh, S. C. Integration sites of human papillomavirus 18 DNA sequences on HeLa cell chromosomes. Cytogenet. Cell Genet., 1987, 44, 58-62.
63. Feitelson, M. A.; Lee, J. Hepatitis B virus integration, fragile sites, and hepatocarcinogenesis. Cancer Lett., 2007, 252, 157-170.
64. Popescu, N. C.; Chen, M. C.; Simpson, S.; Solinas, S.; DiPaolo, J. A. A Burkitt lymphoma cell line with integrated Epstein-Barr virus at a stable chromosome modification site. Virology, 1993, 195, 248-251.
65. Burrow, A. A.; Williams, L. E.; Pierce, L. C.; Wang, Y. H. Over half of breakpoints in gene pairs involved in cancer-specific recurrent translocations are mapped to human chromosomal fragile sites. BMC Genomics, 2009, 10, 59.
66. Arlt, M. F.; Durkin, S. G.; Ragland, R. L.; Glover, T. W. Common fragile sites as targets for chromosome rearrangements. DNA Repair (Amst), 2006, 5, 1126-1135.
67. Durkin, S. G.; Ragland, R. L.; Arlt, M. F.; Mulle, J. G.; Warren, S. T.; Glover, T. W. Replication stress induces tumor-like microdeletions in FHIT/FRA3B. Proc. Natl. Acad. Sci. USA, 2008, 105, 246-251.
68. Ohta, M.; Inoue, H.; Cotticelli, M. G.; Kastury, K.; Baffa, R.; Palazzo, J.; Siprashvili, Z.; Mori, M.; McCue, P.; Druck, T.; Croce, C. M.; Huebner, K. The FHIT gene, spanning the chromosome 3p14.2 fragile site and renal carcinoma-associated t(3;8) breakpoint, is abnormal in digestive tract cancers. Cell, 1996, 84, 587-597.
69. Nikiforov, Y. E. Thyroid carcinoma: molecular pathways and therapeutic targets. Mod. Pathol., 2008, 21(Suppl 2), S37-43.
70. Arighi, E.; Borrello, M. G.; Sariola, H. RET tyrosine kinase signaling in development and cancer. Cytokine Growth Factor Rev., 2005, 16, 441-467.
71. Santoro, M.; Melillo, R. M.; Fusco, A. RET/PTC activation in papillary thyroid carcinoma: European Journal of Endocrinology Prize Lecture. Eur. J. Endocrinol., 2006, 155, 645-653.
72. Gandhi, M.; Medvedovic, M.; Stringer, J. R.; Nikiforov, Y. E. Interphase chromosome folding determines spatial proximity of genes participating in carcinogenic RET/PTC rearrangements. Oncogene, 2006, 25, 2360-2366.
73. Nikiforova, M. N.; Stringer, J. R.; Blough, R.; Medvedovic, M.; Fagin, J. A.; Nikiforov, Y. E. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science, 2000, 290, 138-141.
74. Smanik, P. A.; Furminger, T. L.; Mazzaferri, E. L.; Jhiang, S. M. Breakpoint characterization of the ret/PTC oncogene in human papillary thyroid carcinoma. Hum. Mol. Genet., 1995, 4, 2313-2318.
75. Schwartz, M.; Zlotorynski, E.; Goldberg, M.; Ozeri, E.; Rahat, A.; le Sage, C.; Chen, B. P.; Chen, D. J.; Agami, R.; Kerem, B. Homologous recombination and nonhomologous end-joining repair pathways regulate fragile site stability. Genes Dev., 2005, 19, 2715-2726.
76. Nikiforova, M. N.; Nikiforov, Y. E. Molecular genetics of thyroid cancer: implications for diagnosis, treatment and prognosis. Expert Rev. Mol. Diagn., 2008, 8, 83-95.
77. Fenton, C. L.; Lukes, Y.; Nicholson, D.; Dinauer, C. A.; Francis, G. L.; Tuttle, R. M. The ret/PTC mutations are common in sporadic papillary thyroid carcinoma of children and young adults. J. Clin. Endocrinol. Metab., 2000, 85, 1170-1175.
78. Horner, M.J.R.L.; Krapcho, M.; Neyman, N.; Aminou, R.; Howlader, N.; Altekruse, S.F.; Feuer, E.J.; Huang, L.; Mariotto, A.; Miller, B.A.; Lewis, D.R.; Eisner, M.P.; Stinchcomb, D.G.; Edwards, B.K., Eds. SEER Cancer Statistics Review, In Bethesda, MD, 1975-2006.
79. Enewold, L.; Zhu, K.; Ron, E.; Marrogi, A. J.; Stojadinovic, A.; Peoples, G. E.; Devesa, S. S. Rising thyroid cancer incidence in the United States by demographic and tumor characteristics, 1980-2005. Cancer Epidemiol. Biomarkers Prev., 2009, 18, 784-791.
80. Yamane, G. K. Cancer incidence in the U.S. Air Force: 1989-2002. Aviat. Space Environ. Med., 2006, 77, 789-794.
81. Zuker, M. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res., 2003, 31, 3406-3415.
82. Fry, M.; Loeb, L. A. The fragile X syndrome d(CGG)n nucleotide repeats form a stable tetrahelical structure. Proc. Natl. Acad. Sci. USA, 1994, 91, 4950-4954.
83. Gacy, A. M.; Goellner, G.; Juranic, N.; Macura, S.; McMurray, C. T. Trinucleotide repeats that expand in human disease form hairpin structures in vitro. Cell, 1995, 81, 533-540.
84. Usdin, K.; Woodford, K. J. CGG repeats associated with DNA instability and chromosome fragility form structures that block DNA synthesis in vitro. Nucleic Acids Res., 1995, 23, 4202-4209.
85. Samadashwily, G. M.; Raca, G.; Mirkin, S. M. Trinucleotide repeats affect DNA replication in vivo. Nat. Genet., 1997, 17, 298-304.
86. Zhang, H.; Freudenreich, C. H. An AT-rich sequence in human common fragile site FRA16D causes fork stalling and chromosome breakage in S. cervisiae. Mol. Cell, 2007, 27, 367-379.
87. Burrow, A. A.; Marullo, A.; Holder, L. R.; Wang, Y. H. Secondary structure formation and DNA instability at fragile site FRA16B. Nucleic Acids Res., 2010, 38, 2865-2877.
88. Cleary, J. D.; Nichol, K.; Wang, Y. H.; Pearson, C. E. Evidence of cis-acting factors in replication-mediated trinucleotide repeat instability in primate cells. Nat. Genet., 2002, 31, 37-46.
89. Rindler, P. M.; Clark, R.M.; Pollard, L.M.; De Biase, I.; Bidichandani, S.I. Replication in mammalian cells recapitulates the locus-specific differences in somatic instability of genomic GAA triplet-repeats. Nucleic Acids Res., 2006, 34, 6352-6361.
90. Edamura, K. N.; Leonard, M.R.; Pearson, C.E. Role of replication and CpG methylation in fragile X syndrome CGG deletions in primate cells. Am. J. Hum. Genet., 2005, 76, 302-311.
91. Shah, S. N.; Opresko, P. L.; Meng, X.; Lee, M. Y.; Eckert, K. A. DNA structure and the Werner protein modulate human DNA polymerase delta-dependent replication dynamics within the common fragile site FRA16D. Nucleic Acids Res., 2010, 38, 1149-1162.
92. Abraham, R. T. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev., 2001, 15, 2177-2196.
93. Cimprich, K. A.; Cortez, D. ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol., 2008, 9, 616-627.
94. Cliby, W. A.; Roberts, C. J.; Cimprich, K. A.; Stringer, C. M.; Lamb, J. R.; Schreiber, S. L.; Friend, S. H. Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints. EMBO J., 1998, 17, 159-169.
95. Cortez, D.; Guntuku, S.; Qin, J.; Elledge, S. J. ATR and ATRIP: partners in checkpoint signaling. Science, 2001, 294, 1713-1716.
96. Nghiem, P.; Park, P. K.; Kim Ys, Y. S.; Desai, B. N.; Schreiber, S. L. ATR is not required for p53 activation but synergizes with p53 in the replication checkpoint. J. Biol. Chem., 2002, 277, 4428-4434.
97. Hammond, E. M.; Denko, N. C.; Dorie, M. J.; Abraham, R. T.; Giaccia, A. J. Hypoxia links ATR and p53 through replication arrest. Mol. Cell. Biol., 2002, 22, 1834-1843.
98. Ragland, R. L.; Arlt, M. F.; Hughes, E. D.; Saunders, T. L.; Glover, T. W. Mice hypomorphic for Atr have increased DNA damage and abnormal checkpoint response. Mamm. Genome, 2009, 20, 375-385.
99. Ozeri-Galai, E.; Schwartz, M.; Rahat, A.; Kerem, B. Interplay between ATM and ATR in the regulation of common fragile site stability. Oncogene, 2008, 27, 2109-2117.
100. Musio, A.; Montagna, C.; Mariani, T.; Tilenni, M.; Focarelli, M. L.; Brait, L.; Indino, E.; Benedetti, P. A.; Chessa, L.; Albertini, A.; Ried, T.; Vezzoni, P. SMC1 involvement in fragile site expression. Hum. Mol. Genet., 2005, 14, 525-533.
101. Howlett, N. G.; Taniguchi, T.; Durkin, S. G.; D'Andrea, A. D.; Glover, T. W. The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability. Hum. Mol. Genet., 2005, 14, 693-701.
102. Zhu, M.; Weiss, R. S. Increased common fragile site expression, cell proliferation defects, and apoptosis following conditional inactivation of mouse Hus1 in primary cultured cells. Mol. Biol. Cell, 2007, 18, 1044-1055.
103. Pirzio, L. M.; Pichierri, P.; Bignami, M.; Franchitto, A. Werner syndrome helicase activity is essential in maintaining fragile site stability. J. Cell Biol., 2008, 180, 305-314.
104. Focarelli, M. L.; Soza, S.; Mannini, L.; Paulis, M.; Montecucco, A.; Musio, A. Claspin inhibition leads to fragile site expression. Genes Chromosomes Cancer, 2009, 48, 1083-1090.
105. Moldovan, G. L.; D'Andrea, A. D. How the fanconi anemia path-way guards the genome. Annu. Rev. Genet., 2009, 43, 223-249.
106. Schoder, C.; Liehr, T.; Velleuer, E.; Wilhelm, K.; Blaurock, N.; Weise, A.; Mrasek, K. New aspects on chromosomal instability: chromosomal break-points in Fanconi anemia patients co-localize on the molecular level with fragile sites. Int. J. Oncol., 2010, 36, 307-312.
107. Chan, K. L.; Palmai-Pallag, T.; Ying, S.; Hickson, I. D. Replication stress induces sister-chromatid bridging at fragile site loci in mitosis. Nat. Cell Biol., 2009, 11, 753-760.
108. Andreassen, P. R.; D'Andrea, A. D.; Taniguchi, T. ATR couples FANCD2 monoubiquitination to the DNA-damage response. Genes Dev., 2004, 18, 1958-1963.
109. Taniguchi, T.; D'Andrea, A. D. The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC. Blood, 2002, 100, 2457-2462.
110. Hays, L. E.; Zodrow, D. M.; Yates, J. E.; Deffebach, M. E.; Jacoby, D. B.; Olson, S. B.; Pankow, J. F.; Bagby, G. C. Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression. Br. J. Cancer, 2008, 98, 1653-1661.
111. Wan, C.; Kulkarni, A.; Wang, Y. H. ATR preferentially interacts with common fragile site FRA3B and the binding requires its kinase activity in response to aphidicolin treatment. Mutat. Res.,2010, 686, 39-46.
112. Cimprich, K. A. Fragile sites: breaking up over a slowdown. Curr. Biol., 2003, 13, R231-3.
113. Sharples, G. J. The X philes: structure-specific endonucleases that resolve Holliday junctions. Mol. Microbiol., 2001, 39, 823-834.