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A Study of Radiation-Induced Instability for the Gene Locus Associated with Intellectual Disorders or Developmental Delays

DOI: 10.4236/abc.2023.134010, PP. 128-142

Keywords: Ionizing Radiation, Multiplex Ligation-Dependent Probe Amplification (MLPA), Intellectual Disability (ID), Developmental Delay (DD), p53 Tumor Suppressor

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Abstract:

Multiplex Ligation-Dependent Probe Amplification (MLPA) was used to study the integrity of the chromosomes for two WIL2-derived lymphoblastoid cell lines (TK6 and WTK1) in the presence and absence of ionizing radiation. WTK1 cells contain a p53 mutation, whereas the TK6 cell line has the native p53 tumor-suppressor gene. Each cell line was isolated pre- and post-irradiation (2 and 3 Gy) and analyzed by MLPA. Using probes that target specific regions on chromosomes associated with a distinct subset of microdeletions and microduplications either established or thought to be responsible for intellectual disability or developmental delay, we have demonstrated that WTK1 and TK6 are not impacted in the same way by irradiation. Instead, each cell line presents its own unique MLPA profile. The most notable differences are the appearance of nine unique probe signals only seen in WTK1 cells. These results are important in the study of how different cell lines can be affected in significantly different ways depending on the presence or absence of wild type p53.

References

[1]  De Benedetti, V., Bennett, W.P., Greenblatt, M.S. and Harris, C.C. (1996) p53 Tumor Suppressor Gene: Implications for Iatrogenic Cancer and Cancer Therapy. Medical and Pediatric Oncology, 27, 2-11.
https://doi.org/10.1002/(SICI)1096-911X(1996)27:1+<2::AID-MPO2>3.0.CO;2-Z
[2]  Greenblatt, M.S., Bennett, W.P., Hollstein, M. and Harris, C.C. (1994) Mutations in the p53 Tumor Suppressor Gene: Clues to Cancer Etiology and Molecular Pathogenesis. Cancer Research, 54, 4855-4878.
[3]  Olivier, M., Eeles, R., Hollstein, M., Khan, M.A., Harris, C.C. and Hainaut, P. (2002) The IARC TP53 Database: New Online Mutation Analysis and Recommendations to Users. Human Mutation, 19, 607-614.
https://doi.org/10.1002/humu.10081
[4]  Duffy, M.J., Synnott, N.C., O’Grady, S. and Crown, J. (2022) Targeting p53 for the Treatment of Cancer. Seminars in Cancer Biology, 79, 58-67.
https://doi.org/10.1016/j.semcancer.2020.07.005
[5]  Williams, A.B. and Schumacher, B. (2016) p53 in the DNA-Damage-Repair Process. Cold Spring Harbor Perspectives in Medicine, 6, a026070.
https://doi.org/10.1101/cshperspect.a026070
[6]  Sancar, A., Lindsey-Boltz, L.A., Unsal-Kaçmaz, K. and Linn, S. (2004) Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints. Annual Review of Biochemistry, 73, 39-85.
https://doi.org/10.1146/annurev.biochem.73.011303.073723
[7]  Albrechtsen, N., Dornreiter, I., Grosse, F., Kim, E., Wiesmüller, L. and Deppert, W. (1999) Maintenance of Genomic Integrity by p53: Complementary Roles for Activated and Non-Activated p53. Oncogene, 18, 7706-7717.
https://doi.org/10.1038/sj.onc.1202952
[8]  Bertrand, P., Rouillard, D., Boulet, A., Levalois, C., Soussi, T. and Lopez, B.S. (1997) Increase of Spontaneous Intrachromosomal Homologous Recombination in Mammalian Cells Expressing a Mutant p53 Protein. Oncogene, 14, 1117-1122.
https://doi.org/10.1038/sj.onc.1200931
[9]  Bill, C.A., Yu, Y., Miselis, N.R., Little, J.B. and Nickoloff, J.A. (1997) A Role for p53 in DNA End Rejoining by Human Cell Extracts. Mutation Research/DNA Repair, 385, 21-29.
https://doi.org/10.1016/S0921-8777(97)00040-2
[10]  Blander, G., Kipnis, J., Leal, J.F., Yu, C.E., Schellenberg, G.D. and Oren, M. (1999) Physical and Functional Interaction between p53 and the Werner’s Syndrome Protein. Journal of Biological Chemistry, 274, 29463-29469.
https://doi.org/10.1074/jbc.274.41.29463
[11]  Dudenhöffer, C., Kurth, M., Janus, F., Deppert, W. and Wiesmüller, L. (1999) Dissociation of the Recombination Control and the Sequence-Specific Transactivation Function of P53. Oncogene, 18, 5773-5784.
https://doi.org/10.1038/sj.onc.1202964
[12]  Mathonnet, G., Leger, C., Desnoyers, J., Drouin, R., Therrien, J.P. and Drobetsky, E.A. (2003) UV Wavelength-Dependent Regulation of Transcription-Coupled Nucleotide Excision Repair in p53-Deficient Human Cells. Proceedings of the National Academy of Sciences of the United States of America, 100, 7219-7224.
https://doi.org/10.1073/pnas.1232161100
[13]  Mekeel, K.L., Tang, W., Kachnic, L.A., Luo, C.M., DeFrank, J.S. and Powell, S.N. (1997) Inactivation of p53 Results in High Rates of Homologous Recombination. Oncogene, 14, 1847-1857.
https://doi.org/10.1038/sj.onc.1201143
[14]  Romanova, L.Y., Willers, H., Blagosklonny, M.V. and Powell, S.N. (2004) The Interaction of p53 with Replication Protein A Mediates Suppression of Homologous Recombination. Oncogene, 23, 9025-9033.
https://doi.org/10.1038/sj.onc.1207982
[15]  Saintigny, Y., Rouillard, D., Chaput, B., Soussi, T. and Lopez, B.S. (1999) Mutant p53 Proteins Stimulate Spontaneous and Radiation-Induced Intrachromosomal Homologous Recombination Independently of the Alteration of the Transactivation Activity and of the G1 Checkpoint. Oncogene, 18, 3553-3563.
https://doi.org/10.1038/sj.onc.1202941
[16]  Stürzbecher, H.W., Donzelmann, B., Henning, W., Knippschild, U. and Buchhop, S. (1996) p53 Is Linked Directly to Homologous Recombination Processes via RAD51/RecA Protein Interaction. The EMBO Journal, 15, 1992-2002.
https://doi.org/10.1002/j.1460-2075.1996.tb00550.x
[17]  Tang, W., Willers, H. and Powell, S.N. (1999) p53 Directly Enhances Rejoining of DNA Double-Strand Breaks with Cohesive Ends in γ-Irradiated Mouse Fibroblasts. Cancer Research, 59, 2562-2565.
[18]  Willers, H., et al. (2000) Dissociation of p53-Mediated Suppression of Homologous Recombination from G1/S Cell Cycle Checkpoint Control. Oncogene, 19, 632-639.
https://doi.org/10.1038/sj.onc.1203142
[19]  Zurer, I., et al. (2004) The Role of p53 in Base Excision Repair following Genotoxic Stress. Carcinogenesis, 25, 11-19.
https://doi.org/10.1093/carcin/bgg186
[20]  Lengauer, C., Kinzler, K.W. and Vogelstein, B. (1997) Genetic Instability in Colorectal Cancers. Nature, 386, 623-627.
https://doi.org/10.1038/386623a0
[21]  Lengauer, C., Kinzler, K.W. and Vogelstein, B. (1998) Genetic Instabilities in Human Cancers. Nature, 396, 643-649.
https://doi.org/10.1038/25292
[22]  Negrini, S., Gorgoulis, V.G. and Halazonetis, T.D. (2010) Genomic Instability—An Evolving Hallmark of Cancer. Nature Reviews Molecular Cell Biology, 11, 220-228.
https://doi.org/10.1038/nrm2858
[23]  Matsuno, Y., et al. (2019) Replication Stress Triggers Microsatellite Destabilization and Hypermutation Leading to Clonal Expansion in vitro. Nature Communications, 10, Article No. 3925.
https://doi.org/10.1038/s41467-019-11760-2
[24]  Matsuno, Y., et al. (2021) Replication-Stress-Associated DSBs Induced by Ionizing Radiation Risk Genomic Destabilization and Associated Clonal Evolution. iScience, 24, Article ID: 102313.
https://doi.org/10.1016/j.isci.2021.102313
[25]  Rajagopalan, H. and Lengauer, C. (2004) Aneuploidy and Cancer. Nature, 432, 338-341.
https://doi.org/10.1038/nature03099
[26]  Korbel, J.O. and Campbell, P.J. (2013) Criteria for Inference of Chromothripsis in Cancer Genomes. Cell, 152, 1226-1236.
https://doi.org/10.1016/j.cell.2013.02.023
[27]  Bishop, A.J.R. and Schiestl, R.H. (2002) Homologous Recombination and Its Role in Carcinogenesis. BioMed Research International, 2, Article ID: 798128.
https://doi.org/10.1155/S1110724302204052
[28]  Hoeijmakers, J.H.J. (2009) DNA Damage, Aging, and Cancer. The New England Journal of Medicine, 361, 1475-1485.
https://doi.org/10.1056/NEJMra0804615
[29]  Ciccia, A. and Elledge, S.J. (2010) The DNA Damage Response: Making It Safe to Play with Knives. Molecular Cell, 40, 179-204.
https://doi.org/10.1016/j.molcel.2010.09.019
[30]  Sebastian, R. and Raghavan, S.C. (2016) Induction of DNA Damage and Erroneous Repair Can Explain Genomic Instability Caused by Endosulfan. Carcinogenesis, 37, 929-940.
https://doi.org/10.1093/carcin/bgw081
[31]  Levy, J.A., Virolainen, M. and Defendi, V. (1968) Human Lymphoblastoid Lines from Lymph Node and Spleen. Cancer, 22, 517-524.
https://doi.org/10.1002/1097-0142(196809)22:3<517::AID-CNCR2820220305>3.0.CO;2-A
[32]  Chuang, Y.Y., Chen, Q., Brown, J.P., Sedivy, J.M. and Liber, H.L. (1999) Radiation-Induced Mutations at the Autosomal Thymidine Kinase Locus Are Not Elevated in p53-Null Cells. Cancer Research, 59, 3073-3076.
[33]  Little, J.B., Nagasawa, H., Keng, P.C., Yu, Y. and Li, C.Y. (1995) Absence of Radiation-Induced G1 Arrest in Two Closely Related Human Lymphoblast Cell Lines That Differ in p53 Status. Journal of Biological Chemistry, 270, 11033-11036.
https://doi.org/10.1074/jbc.270.19.11033
[34]  Xia, F., et al. (1995) Altered p53 Status Correlates with Differences in Sensitivity to Radiation-Induced Mutation and Apoptosis in Two Closely Related Human Lymphoblast Lines. Cancer Research, 55, 12-15.
[35]  Peng, Y., Zhang, Q., Nagasawa, H., Okayasu, R., Liber, H.L. and Bedford, J.S. (2002) Silencing Expression of the Catalytic Subunit of DNA-Dependent Protein Kinase by Small Interfering RNA Sensitizes Human Cells for Radiation-Induced Chromosome Damage, Cell Killing, and Mutation. Cancer Research, 62, 6400-6404.
[36]  Amundson, S.A., Xia, F., Wolfson, K. and Liber, H.L. (1993) Different Cytotoxic and Mutagenic Responses Induced by X-Rays in Two Human Lymphoblastoid Cell Lines Derived from a Single Donor. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 286, 233-241.
https://doi.org/10.1016/0027-5107(93)90188-L
[37]  Schouten, J.P., McElgunn, C.J., Waaijer, R., Zwijnenburg, D., Diepvens, F. and Pals, G. (2002) Relative Quantification of 40 Nucleic Acid Sequences by Multiplex Ligation-Dependent Probe Amplification. Nucleic Acids Research, 30, e57.
https://doi.org/10.1093/nar/gnf056
[38]  Kjaergaard, S., et al. (2010) Diagnostic Yield by Supplementing Prenatal Metaphase Karyotyping with MLPA for Microdeletion Syndromes and Subtelomere Imbalances. Prenatal Diagnosis, 30, 995-999.
https://doi.org/10.1002/pd.2604
[39]  Kirchhoff, M., Bisgaard, A.M., Bryndorf, T. and Gerdes, T. (2007) MLPA Analysis for a Panel of Syndromes with Mental Retardation Reveals Imbalances in 5.8% of Patients with Mental Retardation and Dysmorphic Features, Including Duplications of the Sotos Syndrome and Williams—Beuren Syndrome Regions. European Journal of Medical Genetics, 50, 33-42.
https://doi.org/10.1016/j.ejmg.2006.10.002
[40]  Jehee, F.S., et al. (2011) Using a Combination of MLPA Kits to Detect Chromosomal Imbalances in Patients with Multiple Congenital Anomalies and Mental Retardation Is a Valuable Choice for Developing Countries. European Journal of Medical Genetics, 54, e425-432.
https://doi.org/10.1016/j.ejmg.2011.03.007
[41]  Zhang, Q., Liu, Y., Zhou, J., Chen, W., Zhang, Y. and Liber, H.L. (2007) Wild-Type p53 Reduces Radiation Hypermutability in p53-Mutated Human Lymphoblast Cells. Mutagenesis, 22, 329-334.
https://doi.org/10.1093/mutage/gem021
[42]  Kato, S., et al. (2003) Understanding the Function-Structure and Function-Mutation Relationships of p53 Tumor Suppressor Protein by High-Resolution Missense Mutation Analysis. Proceedings of the National Academy of Sciences of the United States of America, 100, 8424-8429.
https://doi.org/10.1073/pnas.1431692100
[43]  Haupt, Y., Maya, R., Kazaz, A. and Oren, M. (1997) Mdm2 Promotes the Rapid Degradation of p53. Nature, 387, 296-299.
https://doi.org/10.1038/387296a0
[44]  Midgley, C.A. and Lane, D.P. (1997) p53 Protein Stability in Tumour Cells Is Not Determined by Mutation But Is Dependent on Mdm2 Binding. Oncogene, 15, 1179-1189.
https://doi.org/10.1038/sj.onc.1201459
[45]  Wiech, M., Olszewski, M.B., Tracz-Gaszewska, Z., Wawrzynow, B., Zylicz, M. and Zylicz, A. (2012) Molecular Mechanism of Mutant p53 Stabilization: The Role of HSP70 and MDM2. PLOS ONE, 7, e51426.
https://doi.org/10.1371/journal.pone.0051426

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