Spontaneous γH2AX foci in human solid tumor-derived cell lines in relation to p21WAF1 and WIP1 expression

International Journal of Molecular Sciences

Volumn 16, Issue 5, 2015, Pages 11609-11628

  Mirzayans, Razmik ^a   Andrais, Bonnie ^a   Scott, April ^a   Wang, Ying W ^a   Weiss, Robert H ^b,c   Murray, David ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Apoptosis; P21WAF1; P53; WIP1; H2AX foci

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 1; HISTONE H2AX; LIPOCORTIN 5; PROTEIN; ROSCOVITINE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; WILD TYPE P53 INDUCED PHOSPHATASE 1; CDKN1A PROTEIN, HUMAN; CYCLIN DEPENDENT KINASE INHIBITOR 1A; HISTONE; PHOSPHOPROTEIN PHOSPHATASE; PPM1D PROTEIN, HUMAN; PROTEIN PHOSPHATASE 2C;

APOPTOSIS; ARTICLE; CELL CULTURE; CELL PROLIFERATION; CELL VIABILITY; COMET ASSAY; CONTROLLED STUDY; DOUBLE STRANDED DNA BREAK; ENZYME INHIBITION; FLOW CYTOMETRY; GENE SILENCING; GENETIC TRANSFECTION; GENOMIC INSTABILITY; HCT116 CELL LINE; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOFLUORESCENCE MICROSCOPY; MCF 7 CELL LINE; PROPIDIUM IODIDE ASSAY; PROTEIN DEPHOSPHORYLATION; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS REGULATION; SOLID TUMOR; DNA REPAIR; GENE DELETION; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; NEOPLASM; PHOSPHORYLATION; TUMOR CELL LINE;

APOPTOSIS; CELL LINE, TUMOR; CYCLIN-DEPENDENT KINASE INHIBITOR P21; DNA BREAKS, DOUBLE-STRANDED; DNA REPAIR; GENE DELETION; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE KNOCKDOWN TECHNIQUES; GENOMIC INSTABILITY; HISTONES; HUMANS; NEOPLASMS; PHOSPHOPROTEIN PHOSPHATASES; PHOSPHORYLATION; PROTEIN PHOSPHATASE 2C;

EID: 84930621914     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms160511609     Document Type: Article

References (61)

1. Fernandez-Capetillo, O.; Lee, A.; Nussenzweig, M.; Nussenzweig, A. H2AX: The histone guardian of the genome. DNA Repair 2004, 3, 959-967.
2. Podhorecka, M.; Skladanowski, A.; Bozko, P. H2AX phosphorylation: Its role in DNA damage response and cancer therapy. J. Nucleic Acids 2010, 2010, 920161.
3. Pilch, D.R.; Sedelnikova, O.A.; Redon, C.; Celeste, A.; Nussenzweig, A.; Bonner, W.M. Characteristics of γ-H2AX foci at DNA double-strand breaks sites. Biochem. Cell Biol. 2003, 81, 123-129.
4. Mirzayans, R.; Severin, D.; Murray, D. Relationship between DNA double-strand break rejoining and cell survival after exposure to ionizing radiation in human fibroblast strains with differing ATM/p53 status: Implications for evaluation of clinical radiosensitivity. Int. J. Radiat. Oncol. Biol. Phys. 2006, 66, 1498-1505.
5. Kuo, L.J.; Yang, L.X. Gamma-H2AX—A novel biomarker for DNA double-strand breaks. In Vivo 2008, 22, 305-309.
6. Wang, M.; Morsbach, F.; Sander, D.; Gheorghiu, L.; Nanda, A.; Benes, C.; Kriegs, M.; Krause, M.; Dikomey, E.; Baumann, M.; et al. EGF receptor inhibition radiosensitizes NSCLC cells by inducing senescence in cells sustaining DNA double-strand breaks. Cancer Res. 2011, 71, 6261-6269.
7. Macůrek, L.; Lindqvist, A.; Voets, O.; Kool, J.; Vos, H.R.; Medema, R.H. WIP1 phosphatase is associated with chromatin and dephosphorylates γH2AX to promote checkpoint inhibition. Oncogene 2010, 29, 2281-2291.
8. Moon, S.H.; Lin, L.; Zhang, X.; Nguyen, T.A.; Darlington, Y.; Waldman, A.S.; Lu, X.; Donehower, L.A. Wild-type p53-induced phosphatase 1 dephosphorylates histone variant γ-H2AX and suppresses DNA double strand break repair. J. Biol. Chem. 2010, 285, 12935-22947.
9. Cha, H.; Lowe, J.M.; Li, H.; Lee, J.S.; Belova, G.I.; Bulavin, D.V.; Fornace, A.J., Jr. WIP1 directly dephosphorylates γ-H2AX and attenuates the DNA damage response. Cancer Res. 2010, 70, 4112-4122.
10. Rogakou, E.P.; Nieves-Neira, W.; Boon, C.; Pommier, Y.; Bonner, W.M. Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J. Biol. Chem. 2000, 275, 9390-9395.
11. Mukherjee, B.; Kessinger, C.; Kobayashi, J.; Chen, B.P.; Chen, D.J.; Chatterjee, A.; Burma, S. DNA-PK phosphorylates histone H2AX during apoptotic DNA fragmentation in mammalian cells. DNA Repair 2006, 5, 575-590.
12. Di Fagagna, F.A.; Reaper, P.M.; Clay-Farrace, L.; Fiegler, H.; Carr, P.; von Zglinicki. T.; Saretzki, G.; Carter, N.P.; Jackson, S.P. A DNA damage checkpoint response in telomere-initiated senescence. Nature 2003, 426, 194-198.
13. Sedelnikova, O.A.; Horikawa, I.; Zimonjic, D.B.; Popescu, N.C.; Bonner, W.M.; Barrett, J.C. Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nat. Cell Biol. 2004, 6, 168-170.
14. Von Zglinicki, T.; Saretzki, G.; Ladhoff, J.; di Fagagna, F.A.; Jackson, S.P. Human cell senescence as a DNA damage response. Mech. Ageing Dev. 2005, 126, 111-117.
15. Di Fagagna, F.A. Living on a break: Cellular senescence as a DNA-damage response. Nat. Rev. Cancer 2008, 8, 512-522.
16. Yu, T.; MacPhail, S.H.; Banáth, J.P.; Klokov, D.; Olive, P.L. Endogenous expression of phosphorylated histone H2AX in tumors in relation to DNA double-strand breaks and genomic instability. DNA Repair 2006, 5, 935-946.
17. Mirzayans, R.; Andrais, B.; Scott, A.; Wang, Y.W.; Murray, D. Ionizing radiation-induced responses in human cells with differing TP53 status. Int. J. Mol. Sci. 2013, 14, 22409-22435.
18. Harper, J.W.; Adami, G.R.; Wei, G.N.; Keyomarsi, K.; Elledge, S.J. The p21 CDK-interacting protein CIP1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 1993, 75, 805-816.
19. Xiong, Y.; Hannon, G.J.; Zhang, H.; Casso, D.; Kobayashi, R.; Beach, D. p21 is a universal inhibitor of cyclin kinases. Nature 1993, 366, 701-704.
20. Warfel, N.A.; El-Deiry, W.S. p21 and tumourigenesis: 20 years after. Curr. Opin. Oncol. 2013, 25, 52-58.
21. Mirzayans, R.; Andrais, B.; Scott, A.; Murray, D. New insights into p53 signaling and cancer-cell response to DNA damage: Implications for cancer therapy. J. Biomed. Biotechnol. 2012, 2012, 170325.
22. Kreis, N.N.; Louwen, F.; Yuan, J. Less understood issues: p21 CIP1 in mitosis and its therapeutic potential. Oncogene 2015, 34, 1758-1767.
23. Song, J.Y.; Ryu, S.H.; Cho, Y.M.; Kim, Y.S.; Lee, B.M.; Lee, S.W.; Choi, J. WIP1 suppresses apoptotic cell death through direct dephosphorylation of BAX in response to γ-radiation. Cell Death Dis. 2013, 4, e744.
24. Han, Z.; Wei, W.; Dunaway, S.; Darnowski, J.W.; Calabresi, P.; Sedivy, J.; Hendrickson, E.A.; Balan, K.V.; Pantazis, P.; Wyche, J.H. Role of p21 in apoptosis and senescence of human colon cancer cells treated with camptothecin. J. Biol. Chem. 2002, 277, 17154-17160.
25. Mirzayans, R.; Scott, A.; Cameron, M.; Murray, D. Induction of accelerated senescence following exposure to ionizing radiation in human solid tumor-derived cell lines expressing wild-type TP53. Radiat. Res. 2005, 163, 53-62.
26. Sohn, D.; Essmann, F.; Schulze-Osthoff, K.; Jänicke, R.U. p21 blocks irradiation-induced apoptosis downstream of mitochondria by inhibition of cyclin-dependent kinase-mediated caspase-9 activation. Cancer Res. 2006, 66, 11254-11262.
27. Sliwinska, M.A.; Mosieniak, G.; Wolanin, K.; Babik, A.; Piwocka, K.; Magalska, A.; Szczepanowska, J.; Fronk, J.; Sikora, E. Induction of senescence with doxorubicin leads to increased genomic instability of HCT116 cells. Mech. Ageing Dev. 2009, 130, 24-32.
28. ARF and p53 levels and an alteration of the Bax/Bcl-2 ratio. J. Biol. Chem. 2002, 277, 37849-37954.
29. WAF1/CIP1 expression exhibit normal nucleotide excision repair of UV-induced DNA damage. Carcinogenesis 2002, 23, 403-410.
30. WAF1/CIP1/SDI1 mediates retinoblastoma protein degradation. Oncogene 2007, 26, 6954-6958.
31. Hill, R.; Leidal, A.M.; Madureira, P.A.; Gillis, L.D.; Waisman, D.M.; Chiu, A.; Lee, P.W. Chromium-mediated apoptosis: Involvement of DNA-dependent protein kinase (DNA-PK) and differential induction of p53 target genes. DNA Repair 2008, 7, 1484-1499.
32. WAF1 are hypersensitive to tyrosine kinase inhibitors and adriamycin through a mechanism unrelated to p21 and dependent on p53. DNA Repair 2009, 8, 390-399.
33. Marti, T.M.; Hefner, E.; Feeney, L.; Natale, V.; Cleaver, J.E. H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double strand breaks. Proc. Natl. Acad. Sci. USA 2006, 103, 9891-9896.
34. Anderson, D.; Andrais, B.; Mirzayans, R.; Siegbahn, E.A.; Fallone, B.G.; Warkentin, B. Comparison of two methods for measuring H2AX nuclear fluorescence as a marker of DNA damage in cultured human cells: Applications for microbeam radiation therapy. J. Instrum. 2013, 8, C06008.
35. WAF1 is component of a positive feedback loop that maintains the p53 transcriptional program. Cell Cycle 2011, 10, 932-950.
36. INK4a
37. WAF1 expression suggests distinct mechanisms of senescence in normal human and Li-Fraumeni Syndrome fibroblasts. J. Cell. Physiol. 2010, 223, 57-67.
38. INK4A in replicative senescence and DNA damage-induced premature senescence in p53-deficient human cells. Biochem. Res. Int. 2012, 2012, 95-1574.
39. Myohanen, S.K.; Baylin, S.B.; Herman, J.G. Hypermethylation can selectively silence individual P16 INK4a alleles in neoplasia. Cancer Res. 1998, 58, 591-593.
40. Haldar, S.; Negrini, M.; Monne, M.; Sabbioni, S.; Croce, C.M. Down-regulation of Bcl-2 by p53 in breast cancer cells. Cancer Res. 1994, 54, 2095-2097.
41. Ramljak, D.; Romanczyk, L.J.; Metheny-Barlow, L.J.; Thompson, N.; Knezevic, V.; Galperin, M.; Ramesh, A.; Dickson, R.B. Pentameric procyanidin from Theobroma cacao selectively inhibits growth of human breast cancer cells. Mol. Cancer Ther. 2005, 4, 537-546.
42. Chai, Y.; Lee, H.J.; Shaik, A.A.; Nkhata, K.; Xing, C.; Zhang, J.; Jeong, S.J.; Kim, S.H.; Lu, J. Penta-O-galloyl-β-D-glucose induces G1 arrest and DNA replicative S-phase arrest independently of cyclin-dependent kinase inhibitor 1A, cyclin-dependent kinase inhibitor 1B and P53 in human breast cancer cells and is orally active against triple negative xenograft growth. Breast Cancer Res. 2010, 12, R67.
43. Morohaku, K.; Hoshino, Y.; Sasada, H.; Sato, E. Incorporation of phosphatase inhibitor in culture prompts growth initiation of isolated non-growing oocytes. PLoS ONE 2013, 8, e77533.
44. Park, J.Y.; Song, J.Y.; Kim, H.M.; Han, H.S.; Seol, H.S.; Jang, S.J.; Choi, J. p53-Independent expression of wild-type p53-induced phosphatase 1 (WIP1) in methylmethane sulfonate-treated cancer cell lines and human tumors. Int. J. Biochem. Cell Biol. 2012, 44, 896-904.
45. Wettersten, H.I.; Hee, H.S.; Li, C.; Shiu, E.Y.; Wecksler, A.T.; Hammock, B.D.; Weiss, R.H. A Uovel p21 attenuator which is structurally related to sorafenib. Cancer Biol. Ther. 2013, 14, 278-285.
46. Park, J.Y.; Park, S.H.; Weiss, R.H. Disparate effects of roscovitine on renal tubular epithelial cell apoptosis and senescence: Implications for autosomal dominant polycystic kidney disease. Am. J. Nephrol. 2009, 29, 509-515.
47. Braun, F.; Bertin-Ciftci, J.; Gallouet, A.S.; Millour, J.; Juin, P. Serum-nutrient starvation induces cell death mediated by Bax and Puma that is counteracted by p21 and unmasked by Bcl-x(L) inhibition. PLoS ONE 2011, 6, e23577.
48. Mirzayans, R.; Pollock, S.; Scott, A.; Gao, C.Q.; Murray, D. Metabolic labeling of human cells with tritiated nucleosides results in activation of the ATM-dependent p53 signaling pathway and acceleration of DNA repair. Oncogene 2003, 22, 5562-5571.
49. Mirzayans, R.; Scott, A.; Andrais, B.; Pollock, S.; Murray, D. Ultraviolet light exposure triggers nuclear accumulation of p21 WAF1 and accelerated senescence in human normal and nucleotide excision repair-deficient fibroblast strains. J. Cell. Physiol. 2008, 215, 55-67.
50. Xu, L.F.; Ni, J.Y.; Sun, H.L.; Chen, Y.T.; Wu, Y.D. Effects of hypoxia-inducible factor-1α silencing on the proliferation of CBRH-7919 hepatoma cells. World J. Gastroenterol. 2013, 19, 1749-1759.
51. Giovannini, C.; Baglioni, M.; Toaldo, M.B.; Ventrucci, C.; d’Adamo, S.; Cipone, M.; Chieco, P.; Gramantieri, L.; Bolondi, L. Notch3 inhibition enhances sorafenib cytotoxic efficacy by promoting GSK3b phosphorylation and p21 down-regulation in hepatocellular carcinoma. Oncotarget 2013, 4, 1618-1631.
52. Celeste, A.; Petersen, S.; Romanienko, P.J.; Fernandez-Capetillo, O.; Chen, H.T.; Sedelnikova, O.A.; Reina-San-Martin, B.; Coppola, V.; Meffre, E.; Difilippantonio, M.J.; et al. Genomic instability in mice lacking histone H2AX. Science 2002, 296, 922-927.
53. Bartkova, J.; Horejsi, Z.; Koed, K.; Kramer, A.; Tort, F.; Zieger, K.; Guldberg, P.; Sehested, M.; Nesland, J.M.; Lukas, C.; et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005, 434, 864-870.
54. Gorgoulis, V.G.; Vassiliou, L.V.; Karakaidos, P.; Zacharatos, P.; Kotsinas, A.; Liloglou, T.; Venere, M.; Ditullio, R.A., Jr.; Kastrinakis, N.G.; Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 2005, 434, 907-913.
55. Warters, R.L.; Adamson, P.J.; Pond, C.D.; Leachman, S.A. Melanoma cells express elevated levels of phosphorylated histone H2AX foci. J. Investig. Dermatol. 2005, 124, 807-817.
56. Perucca, P.; Cazzalini, O.; Mortusewicz, O.; Necchi, D.; Savio, M.; Nardo, T.; Stivala, L.A.; Leonhardt, H.; Cardoso, M.C.; Prosperi, E. Spatiotemporal dynamics of p21CDKN1A protein recruitment to DNA-damage sites and interaction with proliferating cell nuclear antigen. J. Cell Sci. 2006, 119, 1517-1527.
57. Tobias, F.; Durante, M.; Taucher-Scholz, G.; Jakob, B. Spatiotemporal analysis of DNA repair using charged particle radiation. Mutat. Res. 2010, 704, 54-60.
58. Koike, M.; Yutoku, Y.; Accumulation of p21 proteins at DNA damage sites independent of p53 and core NHEJ factors following irradiation. Biochem. Biophys. Res. Commun. 2011, 412, 39-43.
59. Mauro, M.; Rego, M.A.; Boisvert, R.A.; Esashi, F.; Cavallo, F.; Jasin, M.; Howlett, N.G. p21 promotes error-free replication-coupled DNA double-strand break repair. Nucleic Acids Res. 2012, 40, 8348-8360.
60. Lu, X.; Nannenga, B.; Donehower, L. A. PPM1D dephosphorylates CHK1 and p53 and abrogates cell cycle checkpoints. Genes Dev. 2005, 19, 1162-1174.
61. Batchelor, E.; Mock, C.S.; Bhan, I.; Loewer, A.; Lahav, G. Recurrent initiation: A mechanism for triggering p53 pulses in response to DNA damage. Mol. Cell 2008, 9, 277-289.