Micronuclei that are often present in tumor cells are not only the indicator of genetic instability, they also can induce DNA damage during cell progression through the cell cycle. p53 protein is the key regulator of the cell cycle. In this study we compared morphofunctional features of micronuclei depending on the presence of wild-type p53 gene: in human breast adenocarcinoma MCF-7 (p53+) and human epidermoid carcinoma A431 (p53—). The number of cells with MN in these cell lines does not depend on the presence of active p53. However, micronuclei in cell culture with mutant p53 protein more often have lamina defects, carry DNA damage, and generally determine higher risk of tumor progression. Asynchronous with the main nucleus DNA replication in micronuclei in p53+ and p53— cell cultures demonstrates predisposition of cells with micronuclei to chromothripsis.
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Vildanova MS, Savitskaya MA, Onishchenko GE, Smirnova EA. Effect of plant hormones on the components of secretory pathway in human normal and tumor cells. Tsitologiya. 2014;56(7):516-525. Russian.
Kisurina-Evgen’eva OP, Bryantseva SA, Onishchenko GE, Shtil’ AA. Antitubulin agents can initiate different apoptotic pathways. Biophysics. 2006;51(5):771-775.
Savitskaya MA, Vildanova MS, Kisurina-Evgenieva OP, Smirnova EA, Onischenko GE. Mitochondrial pathway of α-tocopheryl succinate-induced apoptosis in human epidermoid carcinoma A431 cells. Acta Naturae. 2012;4(3):88-94.
Chumakov PM. Protein p53 and its universal functions in multicellular organism. Uspekhi Biol. Khimii. 2007;47(1):3-52. Russian.
Asare N, Instanes C, Sandberg WJ, Refsnes M, Schwarze P, Kruszewski M, Brunborg G. Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology. 2012;291(1-3):65-72.
Crasta K, Ganem NJ, Dagher R, Lantermann AB, Ivanova EV, Pan Y, Nezi L, Protopopov A, Chowdhury D, Pellman D. DNA breaks and chromosome pulverization from errors in mitosis. Nature. 2012;482:53-58.
Fenech M, Kirsch-Volders M, Natarajan AT, Surralles J, Crott JW, Parry J, Norppa H, Eastmond DA, Tucker JD, Thomas P. Molecular mechanisms of micronucleus, nucleoplasmic bridge and nuclear bud formation in mammalian and human cells. Mutagenesis. 2011;26(1):125-132.
Hatch EM, Fischer AH, Deerinck TJ, Hetzer MW. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell. 2013;154(1):47-60.
Ly P, Cleveland DW. Rebuilding chromosomes after catastrophe: emerging mechanisms of chromothripsis. Trends Cell Biol. 2017;27(12):917-930.
Morrison AJ, Shen X. DNA repair in the context of chromatin. Cell Cycle. 2005;4(4):568-571.
Park DJ, Nakamura H, Chumakov AM, Said JW, Miller CW, Chen DL, Koeffler HP. Transactivational and DNA binding abilities of endogenous p53 in p53 mutant cell lines. Oncogene. 1994;9(7):1899-1906.
Sablina AA, Ilyinskaya GV, Rubtsova SN, Agapova LS, Chumakov PM, Kopnin BP. Activation of p53-mediated cell cycle checkpoint in response to micronuclei formation. Сell. 1998;111(Pt 7):977-984.
Zhang CZ, Spektor A, Cornils H, Francis JM, Jackson EK, Liu S, Meyerson M, Pellman D. Chromothripsis from DNA damage in micronuclei. Nature. 2015;522:179-184.
Zuela N, Bar DZ, Gruenbaum Y. Lamins in development, tissue maintenance and stress. EMBO Rep. 2012;13(12):1070-1078.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 6, pp. 777-782, June, 2019
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Sutyagina, O.I., Kisurina-Evgenieva, O.P. Morphofunctional Differences of Micronuclei in Cultures of Human p53-Positive and p53-Negative Tumor Cells. Bull Exp Biol Med 167, 813–817 (2019). https://doi.org/10.1007/s10517-019-04629-3
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DOI: https://doi.org/10.1007/s10517-019-04629-3