Browse > Article

Drosophila melanogaster: a Model for the Study of DNA Damage Checkpoint Response  

Song, Young-Han (Ilsong Institute of Life Science, Hallym University)
Abstract
The cells of metazoans respond to DNA damage by either arresting their cell cycle in order to repair the DNA, or by undergoing apoptosis. This response is highly conserved across species, and many of the genes involved in this DNA damage response have been shown to be inactivated in human cancers. This suggests the importance of DNA damage response with regard to the prevention of cancer. The DNA damage checkpoint responses vary greatly depending on the developmental context, cell type, gene expression profile, and the degree and nature of the DNA lesions. More valuable information can be obtained from studies utilizing whole organisms in which the molecular basis of development has been well established, such as Drosophila. Since the discovery of the Drosophila p53 orthologue, various aspects of DNA damage responses have been studied in Drosophila. In this review, I will summarize the current knowledge on the DNA damage checkpoint response in Drosophila. With the ease of genetic, cellular, and cytological approaches, Drosophila will become an increasingly valuable model organism for the study of mechanisms inherent to cancer formation associated with defects in the DNA damage pathway.
Keywords
Apoptosis; Cancer; Cell Cycle; Checkpoint; DNA Damage; Drosophila;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 24  (Related Records In Web of Science)
연도 인용수 순위
1 Andreassen, P. R., Lacroix, F. B., Lohez, O. D., and Margolis, R. L. (2001) Neither p21WAF1 nor 14-3-3sigma prevents G2 progression to mitotic catastrophe in human colon carcinoma cells after DNA damage, but p21WAF1 induces stable G1 arrest in resulting tetraploid cells. Cancer Res. 61, 7660-7668
2 Baker, B. S. and Carpenter, A. T. (1972) Genetic analysis of sex chromosomal meiotic mutants in Drosophilia melanogaster. Genetics 71, 255-286
3 Bartek, J. and Lukas, J. (2003) Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3, 421-429   DOI   ScienceOn
4 Brodsky, M. H., Sekelsky, J. J., Tsang, G., Hawley, R. S., and Rubin, G. M. (2000a) mus304 encodes a novel DNA damage checkpoint protein required during Drosophila development. Genes Dev. 14, 666-678
5 Callen, E. and Surralles, J. (2004) Telomere dysfunction in genome instability syndromes. Mutat. Res. 567, 85-104   DOI   ScienceOn
6 Cenci, G., Siriaco, G., Raffa, G. D., Kellum, R., and Gatti, M. (2003) The Drosophila HOAP protein is required for telomere capping. Nat. Cell. Biol. 5, 82-84   DOI   ScienceOn
7 Gurley, L. R., D'Anna, J. A., Barham, S. S., Deaven, L. L., and Tobey, R. A. (1978) Histone phosphorylation and chromatin structure during mitosis in Chinese hamster cells. Eur. J. Biochem. 84, 1-15   DOI   ScienceOn
8 Kockel, L., Vorbruggen, G., Jackle, H., Mlodzik, M., and Bohmann, D. (1997) Requirement for Drosophila 14-3-3 zeta in Raf-dependent photoreceptor development. Genes Dev. 11, 1140-1147   DOI   ScienceOn
9 Krause, S. A., Loupart, M. L., Vass, S., Schoenfelder, S., Harrison, S., et al. (2001) Loss of cell cycle checkpoint control in Drosophila Rfc4 mutants. Mol. Cell. Biol. 21, 5156-5168   DOI   ScienceOn
10 Lee, Y., Lee, J., Bang, S., Hyun, S., Kang, J., et al. (2005) Pyrexia is a new thermal transient receptor potential channel endowing tolerance to high temperatures in Drosophila melanogaster. Nat. Genet. 37, 305-310   DOI   ScienceOn
11 Nilssen, E. A., Synnes, M., Tvegard, T., Vebo, H., Boye, E., et al. (2004) Germinating fission yeast spores delay in G1 in response to UV irradiation. BMC Cell Biol. 5, 40   DOI   ScienceOn
12 Nordstrom, W., Chen, P., Steller, H., and Abrams, J. M. (1996) Activation of the reaper gene during ectopic cell killing in Drosophila. Dev. Biol. 180, 213-226   DOI   ScienceOn
13 Paulson, J. R. and Taylor, S. S. (1982) Phosphorylation of histones 1 and 3 and nonhistone high mobility group 14 by an endogenous kinase in HeLa metaphase chromosomes. J. Biol. Chem. 257, 6064-6072
14 Sellins, K. S. and Cohen, J. J. (1987) Gene induction by gammairradiation leads to DNA fragmentation in lymphocytes. J. Immunol. 139, 3199-3206
15 Pellicioli, A., Lee, S. E., Lucca, C., Foiani, M., and Haber, J. E. (2001) Regulation of Saccharomyces Rad53 checkpoint kinase during adaptation from DNA damage-induced G2/M arrest. Mol. Cell 7, 293-300   DOI   ScienceOn
16 Royou, A., Macias, H., and Sullivan, W. (2005) The Drosophila Grp/Chk1 DNA damage checkpoint controls entry into anaphase. Curr. Biol. 15, 334-339   DOI   ScienceOn
17 Schmidt-Kastner, P. K., Jardine, K., Cormier, M., and McBurney, M. W. (1998) Absence of p53-dependent cell cycle regulation in pluripotent mouse cell lines. Oncogene 16, 3003-3011   DOI
18 Skoulakis, E. M. and Davis, R. L. (1996) Olfactory learning deficits in mutants for leonardo, a Drosophila gene encoding a 14-3-3 protein. Neuron 17, 931-944   DOI   ScienceOn
19 Smits, V. A., Klompmaker, R., Arnaud, L., Rijksen, G., Nigg, E. A., et al. (2000) Polo-like kinase-1 is a target of the DNA damage checkpoint. Nat. Cell. Biol. 2, 672-676   DOI   ScienceOn
20 Su, T. T., Parry, D. H., Donahoe, B., Chien, C. T., O'Farrell, P. H., et al. (2001) Cell cycle roles for two 14-3-3 proteins during Drosophila development. J. Cell Sci. 114, 3445-3454
21 Wolff, T. and Ready, D. F. (1993) Pattern formation in the Drosophila retina; in The Development of Drosophila melanogaster, Bate, M. and Arias, A. M. (eds.), pp. 1277-1325, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY
22 Yoo, H. Y., Kumagai, A., Shevchenko, A., and Dunphy, W. G. (2004) Adaptation of a DNA replication checkpoint response depends upon inactivation of Claspin by the Polo-like kinase. Cell 117, 575-588   DOI   ScienceOn
23 Siede, W., Friedberg, A. S., and Friedberg, E. C. (1993) RAD9- dependent G1 arrest defines a second checkpoint for damaged DNA in the cell cycle of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 90, 7985-7989
24 White, K., Tahaoglu, E., and Steller, H. (1996) Cell killing by the Drosophila gene reaper. Science 271, 805-807   DOI   ScienceOn
25 Lee, L. A. and Orr-Weaver, T. L. (2003) Regulation of cell cycles in Drosophila development: intrinsic and extrinsic cues. Annu. Rev. Genet. 37, 545-578   DOI   ScienceOn
26 Chan, T. A., Hermeking, H., Lengauer, C., Kinzler, K. W., and Vogelstein, B. (1999) 14-3-3Sigma is required to prevent mitotic catastrophe after DNA damage. Nature 401, 616-620   DOI
27 Pagliarini, R. A. and Xu, T. (2003) A genetic screen in Drosophila for metastatic behavior. Science 302, 1227-1231   DOI   ScienceOn
28 Sekelsky, J. J., Brodsky, M. H., and Burtis, K. C. (2000) DNA repair in Drosophila: insights from the Drosophila genome sequence. J. Cell Biol. 150, F31-36   DOI
29 Shechter, D., Costanzo, V., and Gautier, J. (2004) ATR and ATM regulate the timing of DNA replication origin firing. Nat. Cell Biol. 6, 648-655   DOI   ScienceOn
30 Sibon, O. C., Kelkar, A., Lemstra, W., and Theurkauf, W. E. (2000) DNA-replication/DNA-damage-dependent centrosome inactivation in Drosophila embryos. Nat. Cell. Biol. 2, 90-95   DOI   ScienceOn
31 Xu, J., Xin, S., and Du, W. (2001) Drosophila Chk2 is required for DNA damage-mediated cell cycle arrest and apoptosis. FEBS Lett. 508, 394-398   DOI   ScienceOn
32 Cenci, G., Rawson, R. B., Belloni, G., Castrillon, D. H., Tudor, M., et al. (1997) UbcD1, a Drosophila ubiquitin-conjugating enzyme required for proper telomere behavior. Genes Dev. 11, 863-875   DOI   ScienceOn
33 Nyberg, K. A., Michelson, R. J., Putnam, C. W., and Weinert, T. A. (2002) Toward maintaining the genome: DNA damage and replication checkpoints. Annu. Rev. Genet. 36, 617-656   DOI   ScienceOn
34 Pagliarini, R. A., Quinones, A. T., and Xu, T. (2003) Analyzing the function of tumor suppressor genes using a Drosophila model. Methods Mol. Biol. 223, 349-382
35 Queiroz-Machado, J., Perdigao, J., Simoes-Carvalho, P., Herrmann, S., and Sunkel, C. E. (2001) tef: a mutation that causes telomere fusion and severe genome rearrangements in Drosophila melanogaster. Chromosoma 110, 10-23   DOI
36 Tapon, N., Harvey, K. F., Bell, D. W., Wahrer, D. C., Schiripo, T. A., et al. (2002) Salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 110, 467-478   DOI   ScienceOn
37 Castedo, M., Perfettini, J. L., Roumier, T., Andreau, K., Medema, R., et al. (2004) Cell death by mitotic catastrophe: a molecular definition. Oncogene 23, 2825-2837   DOI   ScienceOn
38 Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A. Jr., et al. (1992) Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 356, 215-221   DOI   ScienceOn
39 Jaklevic, B. R. and Su, T. T. (2004) Relative contribution of DNA repair, cell cycle checkpoints, and cell death to survival after DNA damage in Drosophila larvae. Curr. Biol. 14, 23- 32   DOI   ScienceOn
40 Rouse, J. and Jackson, S. P. (2002) Interfaces between the detection, signaling, and repair of DNA damage. Science 297, 547-551   DOI   ScienceOn
41 Bi, X., Wei, S. C., and Rong, Y. S. (2004) Telomere protection without a telomerase; the role of ATM and Mre11 in Drosophila telomere maintenance. Curr. Biol. 14, 1348-1353   DOI   ScienceOn
42 Davis, T., Meyers, M., Patten, C. W.-V., Sharda, N., Yang, C.-R., et al. (1998) Transcriptional responses to damage created by ionizing radiation. In DNA damage and repair, Nickologg, J. A. and Hoekstra, M. F. (eds.), pp. 223-262, Humana Press Inc., Totowa, New Jersey
43 Fogarty, P., Campbell, S. D., Abu-Shumays, R., Phalle, B. S., Yu, K. R., et al. (1997) The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity. Curr. Biol. 7, 418-426   DOI   ScienceOn
44 Mikhailov, A., Cole, R. W., and Rieder, C. L. (2002) DNA damage during mitosis in human cells delays the metaphase/ anaphase transition via the spindle-assembly checkpoint. Curr. Biol. 12, 1797-1806   DOI   ScienceOn
45 Galgoczy, D. J. and Toczyski, D. P. (2001) Checkpoint adaptation precedes spontaneous and damage-induced genomic instability in yeast. Mol. Cell. Biol. 21, 1710-1718   DOI   ScienceOn
46 Brodsky, M. H., Weinert, B. T., Tsang, G., Rong, Y. S., McGinnis, N. M., et al. (2004) Drosophila melanogaster MNK/Chk2 and p53 regulate multiple DNA repair and apoptotic pathways following DNA damage. Mol. Cell. Biol. 24, 1219-1231   DOI
47 Silva, E., Tiong, S., Pedersen, M., Homola, E., Royou, A., et al. (2004) ATM is required for telomere maintenance and chromosome stability during Drosophila development. Curr. Biol. 14, 1341-1347   DOI   ScienceOn
48 Skoulakis, E. M. and Davis, R. L. (1998) 14-3-3 proteins in neuronal development and function. Mol. Neurobiol. 16, 269-284   DOI   ScienceOn
49 Song, Y. H., Mirey, G., Betson, M., Haber, D. A., and Settleman, J. (2004) The Drosophila ATM ortholog, dATM, mediates the response to ionizing radiation and to spontaneous DNA damage during development. Curr. Biol. 14, 1354-1359   DOI   ScienceOn
50 Bartek, J., Lukas, C., and Lukas, J. (2004) Checking on DNA damage in S phase. Nat. Rev. Mol. Cell. Biol. 5, 792-804   DOI   ScienceOn
51 Ciapponi, L., Cenci, G., Ducau, J., Flores, C., Johnson-Schlitz, D., et al. (2004) The Drosophila Mre11/Rad50 complex is required to prevent both telomeric fusion and chromosome breakage. Curr. Biol. 14, 1360-1366   DOI   ScienceOn
52 Lanni, J. S. and Jacks, T. (1998) Characterization of the p53- dependent postmitotic checkpoint following spindle disruption. Mol. Cell. Biol. 18, 1055-1064
53 Chang, H. C. and Rubin, G. M. (1997) 14-3-3 epsilon positively regulates Ras-mediated signaling in Drosophila. Genes Dev. 11, 1132-1139   DOI   ScienceOn
54 Falck, J., Petrini, J. H., Williams, B. R., Lukas, J., and Bartek, J. (2002) The DNA damage-dependent intra-S phase checkpoint is regulated by parallel pathways. Nat. Genet. 30, 290- 294   DOI   ScienceOn
55 Rong, Y. S., Titen, S. W., Xie, H. B., Golic, M. M., Bastiani, M., et al. (2002) Targeted mutagenesis by homologous recombination in D. melanogaster. Genes Dev. 16, 1568-1581   DOI   ScienceOn
56 Xu, J. and Du, W. (2003) Drosophila chk2 plays an important role in a mitotic checkpoint in syncytial embryos. FEBS Lett. 545, 209-212   DOI   ScienceOn
57 Zhou, B. B. and Elledge, S. J. (2000) The DNA damage response: putting checkpoints in perspective. Nature 408, 433- 439   DOI   ScienceOn
58 Sibon, O. C., Stevenson, V. A., and Theurkauf, W. E. (1997) DNA-replication checkpoint control at the Drosophila midblastula transition. Nature 388, 93-97   DOI   ScienceOn
59 Sibon, O. C., Laurencon, A., Hawley, R., and Theurkauf, W. E. (1999) The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. Curr. Biol. 9, 302-312   DOI   ScienceOn
60 Abraham, R. T. (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev. 15, 2177-2196   DOI   ScienceOn
61 Kastan, M. B. and Bartek, J. (2004) Cell-cycle checkpoints and cancer. Nature 432, 316-323   DOI   ScienceOn
62 Oishi, I., Sugiyama, S., Otani, H., Yamamura, H., Nishida, Y., et al. (1998) A novel Drosophila nuclear protein serine/threonine kinase expressed in the germline during its establishment. Mech. Dev. 71, 49-63   DOI   ScienceOn
63 Ollmann, M., Young, L. M., Di Como, C. J., Karim, F., Belvin, M., et al. (2000) Drosophila p53 is a structural and functional homolog of the tumor suppressor p53. Cell 101, 91-101   DOI   ScienceOn
64 Boyd, J. B., Golino, M. D., Nguyen, T. D., and Green, M. M. (1976) Isolation and characterization of X-linked mutants of Drosophila melanogaster which are sensitive to mutagens. Genetics 84, 485-506
65 Fanti, L., Giovinazzo, G., Berloco, M., and Pimpinelli, S. (1998) The heterochromatin protein 1 prevents telomere fusions in Drosophila. Mol. Cell 2, 527-538   DOI   ScienceOn
66 Haynie, J. L. and Bryant, P. J. (1977) The effects of X-rays on the proliferation dynamics of cells in the imaginal wing disc of Drosophila melanogaster. Wilhelm Roux's Archives 183, 85-100   DOI
67 Peterson, C., Carney, G. E., Taylor, B. J., and White, K. (2002) reaper is required for neuroblast apoptosis during Drosophila development. Development 129, 1467-1476
68 Ghabrial, A., Ray, R. P., and Schupbach, T. (1998) okra and spindle-B encode components of the RAD52 DNA repair pathway and affect meiosis and patterning in Drosophila oogenesis. Genes Dev. 12, 2711-2723   DOI
69 Brodsky, M. H., Nordstrom, W., Tsang, G., Kwan, E., Rubin, G. M., et al. (2000b) Drosophila p53 binds a damage response element at the reaper locus. Cell 101, 103-113   DOI   ScienceOn
70 Jassim, O. W., Fink, J. L., and Cagan, R. L. (2003) Dmp53 protects the Drosophila retina during a developmentally regulated DNA damage response. EMBO J. 22, 5622-5632   DOI   ScienceOn
71 Starz-Gaiano, M. and Montell, D. J. (2004) Genes that drive invasion and migration in Drosophila. Curr. Opin. Genet. Dev. 14, 86-91   DOI   ScienceOn
72 Takai, H., Naka, K., Okada, Y., Watanabe, M., Harada, N., et al. (2002) Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. EMBO J. 21, 5195-5205   DOI   ScienceOn
73 Thibault, S. T., Singer, M. A., Miyazaki, W. Y., Milash, B., Dompe, N. A., et al. (2004) A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac. Nat. Genet. 36, 283-287   DOI   ScienceOn
74 Takada, S., Kelkar, A., and Theurkauf, W. E. (2003) Drosophila checkpoint kinase 2 couples centrosome function and spindle assembly to genomic integrity. Cell 113, 87-99   DOI   ScienceOn
75 Hirao, A., Cheung, A., Duncan, G., Girard, P. M., Elia, A. J., et al. (2002) Chk2 is a tumor suppressor that regulates apoptosis in both an ataxia telangiectasia mutated (ATM)- dependent and an ATM-independent manner. Mol. Cell. Biol. 22, 6521-6532   DOI
76 Foe, V. E., Odell, G. M., and Edgar, B. A. (1993) The Development of Drosophila melanogaster, Cold Spring Harbor Laboratory Press, Cold Springer Harbor, NY
77 Peters, M., DeLuca, C., Hirao, A., Stambolic, V., Potter, J., et al. (2002) Chk2 regulates irradiation-induced, p53-mediated apoptosis in Drosophila. Proc. Natl. Acad. Sci. USA 99, 11305-11310
78 Santocanale, C. and Diffley, J. F. (1998) A Mec1- and Rad53- dependent checkpoint controls late-firing origins of DNA replication. Nature 395, 615-618   DOI   ScienceOn
79 Su, T. T. and Jaklevic, B. (2001) DNA damage leads to a Cyclin A-dependent delay in metaphase-anaphase transition in the Drosophila gastrula. Curr. Biol. 11, 8-17   DOI   ScienceOn
80 Su, T. T., Walker, J., and Stumpff, J. (2000) Activating the DNA damage checkpoint in a developmental context. Curr. Biol. 10, 119-126   DOI   ScienceOn
81 White, K., Grether, M. E., Abrams, J. M., Young, L., Farrell, K., et al. (1994) Genetic control of programmed cell death in Drosophila. Science 264, 677-683   DOI
82 Neufeld, T. P., de la Cruz, A. F., Johnston, L. A., and Edgar, B. A. (1998) Coordination of growth and cell division in the Drosophila wing. Cell 93, 1183-1193   DOI   ScienceOn
83 Borel, F., Lohez, O. D., Lacroix, F. B., and Margolis, R. L. (2002) Multiple centrosomes arise from tetraploidy checkpoint failure and mitotic centrosome clusters in p53 and RB pocket protein-compromised cells. Proc. Natl. Acad. Sci. USA 99, 9819-9824
84 de Nooij, J. C., Letendre, M. A., and Hariharan, I. K. (1996) A cyclin-dependent kinase inhibitor, Dacapo, is necessary for timely exit from the cell cycle during Drosophila embryogenesis. Cell 87, 1237-1247   DOI   ScienceOn
85 Manke, I. A., Nguyen, A., Lim, D., Stewart, M. Q., Elia, A. E., et al. (2005) MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation. Mol. Cell 17, 37-48   DOI   ScienceOn
86 Skoufias, D. A., Lacroix, F. B., Andreassen, P. R., Wilson, L., and Margolis, R. L. (2004) Inhibition of DNA decatenation, but not DNA damage, arrests cells at metaphase. Mol. Cell 15, 977-990   DOI   ScienceOn
87 Oikemus, S. R., McGinnis, N., Queiroz-Machado, J., Tukachinsky, H., Takada, S., et al. (2004) Drosophila atm/telomere fusion is required for telomeric localization of HP1 and telomere position effect. Genes Dev. 18, 1850-1861   DOI   ScienceOn
88 Tapon, N., Ito, N., Dickson, B. J., Treisman, J. E., and Hariharan, I. K. (2001) The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105, 345-355   DOI   ScienceOn
89 Zhou, L. and Steller, H. (2003) Distinct pathways mediate UVinduced apoptosis in Drosophila embryos. Dev. Cell 4, 599- 605   DOI   ScienceOn
90 Hari, K. L., Santerre, A., Sekelsky, J. J., McKim, K. S., Boyd, J. B., et al. (1995) The mei-41 gene of D. melanogaster is a structural and functional homolog of the human ataxia telangiectasia gene. Cell 82, 815-821   DOI   ScienceOn
91 McEachern, M. J., Krauskopf, A., and Blackburn, E. H. (2000) Telomeres and their control. Annu. Rev. Genet. 34, 331-358   DOI   ScienceOn
92 Pardue, M. L. and DeBaryshe, P. G. (2003) Retrotransposons provide an evolutionarily robust non-telomerase mechanism to maintain telomeres. Annu. Rev. Genet. 37, 485-511   DOI   ScienceOn
93 Xu, T., Wang, W., Zhang, S., Stewart, R. A., and Yu, W. (1995) Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121, 1053-1063
94 Abdu, U., Brodsky, M., and Schupbach, T. (2002) Activation of a meiotic checkpoint during Drosophila oogenesis regulates the translation of Gurken through Chk2/Mnk. Curr. Biol. 12, 1645-1651   DOI   ScienceOn
95 Brumbaugh, K. M., Otterness, D. M., Geisen, C., Oliveira, V., Brognard, J., et al. (2004) The mRNA surveillance protein hSMG-1 functions in genotoxic stress response pathways in mammalian cells. Mol. Cell 14, 585-598   DOI   ScienceOn
96 Gerald, J. N., Benjamin, J. M., and Kron, S. J. (2002) Robust G1 checkpoint arrest in budding yeast: dependence on DNA damage signaling and repair. J. Cell Sci. 115, 1749-1757
97 Sancar, A., Lindsey-Boltz, L. A., Unsal-Kacmaz, K., and Linn, S. (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73, 39-85   DOI   ScienceOn
98 Bae, I., Smith, M. L., and Fornace, A. J. Jr. (1995) Induction of p53-, MDM2-, and WAF1/CIP1-like molecules in insect cells by DNA-damaging agents. Exp. Cell. Res. 217, 541-545   DOI   ScienceOn
99 Baker, B. S., Carpenter, A. T., and Ripoll, P. (1978) The utilization during mitotic cell division of loci controlling meiotic recombination and disjunction in Drosophila melanogaaster. Genetics 90, 531-578