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Establishment of HindIIIG-1 Cell Line, Obtained after Irradiation of HindIIIG Cells Resistant to Apoptosis, Characterizes by Genomic Instability, Altered DNA Repair Mechanisms and Activation of Autophagy

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Abstract

Genomic instability and heterogeneity are the key features of cancer cells that allow their survival under environmental stress. A rapid accumulation of a large number of mutations in a single event due to a massive rearrangement of fragmented chromosomes termed chromothripsis favors cancer progression and resistance to therapy. Complex chromosomal rearrangements that occur upon chromothripsis arise from a random ligation of multiple chromosome fragments by an error-prone NHEJ DNA repair. Here we studied the activation of DDR and NHEJ as markers of genomic instability in HindIIIG-1 cells obtained after depolyploidization of irradiated HindIIIG cells resistant to apoptosis. We also analyzed the potential involvement of chromothripsis-like mechanism and autophagy in the establishment of HindIIIG-1 cell line. Our results demonstrate that HindIIIG cells are characterized by high genomic instability, activation of DDR and NHEJ. Chromosome fragmentation and activation of NHEJ in irradiated HindIIIG and non-treated HindIIIG-1 cells suggest the implication of chromothripsis-like mechanism in the establishment of HindIIIG-1 cell line. We show that unlike HindIIIG cells, HindIIIG-1 cells acquired invasion ability and adhesion-independent cell growth that may indicate their metastatic potential. Degradation of damaged DNA, nuclei and micronuclei in HindIIIG-1 cells by autophagy suggests its role in cell death and survival and thereby in establishment of novel cell line.

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Funding

The work was supported by budgetary funding of Institute of Cytology, Russian Academy of Sciences.

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Authors and Affiliations

  1. Institute of Cytology RAS, 194064, St. Petersburg, Russia

    N. M. Yartseva, T. V. Bykova, S. G. Zubova, E. Y. Kochetkova, V. A. Pospelov & T. V. Pospelova

  2. Geneva University, 1205, Geneva, Switzerland

    Z. V. Chitikova

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  1. Z. V. Chitikova
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  2. N. M. Yartseva
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  3. T. V. Bykova
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Correspondence to Z. V. Chitikova.

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Chitikova, Z.V., Yartseva, N.M., Bykova, T.V. et al. Establishment of HindIIIG-1 Cell Line, Obtained after Irradiation of HindIIIG Cells Resistant to Apoptosis, Characterizes by Genomic Instability, Altered DNA Repair Mechanisms and Activation of Autophagy. Cell Tiss. Biol. 15, 370–380 (2021). https://doi.org/10.1134/S1990519X2104009X

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