Version 1
: Received: 16 November 2023 / Approved: 17 November 2023 / Online: 17 November 2023 (07:47:41 CET)
How to cite:
Pustovalova, M.; Malakhov, P.; Nofal, Z.; Moroz, I.; Trubchenkova, T.; Gromova, A.; Leonov, S. PRIMPOL and POLI Deficiencies Differentially Affect DNA Repair and Post-Irradiation Survival of Non-Small Cell Lung Cancer Cell Lines. Preprints2023, 2023111139. https://doi.org/10.20944/preprints202311.1139.v1
Pustovalova, M.; Malakhov, P.; Nofal, Z.; Moroz, I.; Trubchenkova, T.; Gromova, A.; Leonov, S. PRIMPOL and POLI Deficiencies Differentially Affect DNA Repair and Post-Irradiation Survival of Non-Small Cell Lung Cancer Cell Lines. Preprints 2023, 2023111139. https://doi.org/10.20944/preprints202311.1139.v1
Pustovalova, M.; Malakhov, P.; Nofal, Z.; Moroz, I.; Trubchenkova, T.; Gromova, A.; Leonov, S. PRIMPOL and POLI Deficiencies Differentially Affect DNA Repair and Post-Irradiation Survival of Non-Small Cell Lung Cancer Cell Lines. Preprints2023, 2023111139. https://doi.org/10.20944/preprints202311.1139.v1
APA Style
Pustovalova, M., Malakhov, P., Nofal, Z., Moroz, I., Trubchenkova, T., Gromova, A., & Leonov, S. (2023). PRIMPOL and POLI Deficiencies Differentially Affect DNA Repair and Post-Irradiation Survival of Non-Small Cell Lung Cancer Cell Lines. Preprints. https://doi.org/10.20944/preprints202311.1139.v1
Chicago/Turabian Style
Pustovalova, M., Anastasia Gromova and Sergey Leonov. 2023 "PRIMPOL and POLI Deficiencies Differentially Affect DNA Repair and Post-Irradiation Survival of Non-Small Cell Lung Cancer Cell Lines" Preprints. https://doi.org/10.20944/preprints202311.1139.v1
Abstract
Radiation therapy (RT) is one of the main approaches of cancer therapy, including non-small cell lung cancer (NSCLC). Radiation-induced DNA double-stranded breaks (DSBs), single-stranded DNA breaks (SSBs) and oxidized nucleobases cause replication fork stalling, chromosomal instability or point mutagenesis and can lead to cell death. Translesion DNA synthesis (TLS) is one of the DNA damage tolerance (DDT) pathways promoting replication of damaged DNA. Here, we explored the effects of the knockout of primase-polymerase PRIMPOL (PRIMPOL −/−) and TLS polymerase POLI (POLI −/−) genes in two different monoclonal lines derived from human NSCLC A549 cells. Our study aimed to investigate the impact of their absence on the susceptibility of these cells to ionizing radiation (IR)-induced stress. Without IR, cells that do not have PRIMPOL or POLI experience a considerable rise in apoptosis by day 7 of continuous cultivation and a noteworthy decline in cell migration under spatial confinement when compared to the parental wild-type cells. Despite this, we have found that PRIMPOL −/− exhibited higher clonogenic survival compared to wild-type cell lines in response to IR stress. Both of these cell lines demonstrated remarkable resilience to radiation stress, surpassing the survival rate of the original A549 cells. POLI deficiency reduces cellular γH2AX foci accumulation, while the presence of highest number of γH2AX foci in PRIMPOL−/− cells was ATM-independent. We report for the first time that increased post-irradiation clonogenic survival of PRIMPOL −/− A549 cells might be associated with the increase of CD133+ but not CD44+ populations of cancer stem-like cells.
Keywords
non-small cell lung cancer; ionizing radiation; DNA repair; PrimPol; DNA damage tolerance; translesion synthesis; Pol iota (Polι); clonogenic survival; cancer stem-like cells
Subject
Biology and Life Sciences, Cell and Developmental Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
