Response of PRIMPOL-Knockout Human Lung Adenocarcinoma A549 Cells to Genotoxic Stress

Human DNA primase/polymerase PrimPol synthesizes DNA primers de novo after replication fork stalling at the sites of DNA damage, thus contributing to the DNA damage tolerance. The role of PrimPol in response to the different types of DNA damage is poorly understood. We knocked out the PRIMPOL gene i...

Full description

Saved in:
Bibliographic Details
Published in:Biochemistry (Moscow) 2023-11, Vol.88 (11), p.1933-1943
Main Authors: Gromova, Anastasia S., Boldinova, Elizaveta O., Kim, Daria V., Chuprov-Netochin, Roman N., Leonov, Sergey V., Pustovalova, Margarita V., Zharkov, Dmitry O., Makarova, Alena V.
Format: Article
Language:English
Subjects:
Adenocarcinoma
Apoptosis
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Bleomycin
Cisplatin
Damage tolerance
Deoxyribonucleic acid
DNA
DNA damage
DNA polymerases
DNA primase
G2 phase
Genetic aspects
Genotoxicity
Health aspects
Hydrogen peroxide
Ionizing radiation
Life Sciences
Lung cancer
Lung carcinoma
Lungs
Methyl methanesulfonate
Microbiology
Necroptosis
Oxidative stress
Primase
Radiation
Radiation dosage
Replication fork
Review
S phase
Stalling
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Human DNA primase/polymerase PrimPol synthesizes DNA primers de novo after replication fork stalling at the sites of DNA damage, thus contributing to the DNA damage tolerance. The role of PrimPol in response to the different types of DNA damage is poorly understood. We knocked out the PRIMPOL gene in the lung carcinoma A549 cell line and characterized the response of the obtained cells to the DNA damage caused by hydrogen peroxide, methyl methanesulfonate (MMS), cisplatin, bleomycin, and ionizing radiation. The PRIMPOL knockout reduced the number of proliferating cells and cells in the G2 phase after treatment with MMS and caused a more pronounced delay of the S phase in the cisplatin-treated cells. Ionizing radiation at a dose of 10 Gy significantly increased the content of apoptotic cells among the PRIMPOL -deficient cells, while the proportion of cells undergoing necroptosis increased in both parental and knockout cells at any radiation dose. The viability of PRIMPOL -deficient cells upon the hydrogen peroxide-induced oxidative stress increased compared to the control cells, as determined by the methyl tetrazolium (MTT) assay. The obtained data indicate the involvement of PRIMPOL in the modulation of adaptive cell response to various types of genotoxic stress.
ISSN:0006-2979
1608-3040
DOI:10.1134/S0006297923110214