PARP1 Gene Knockout Suppresses Expression of DNA Base Excision Repair Genes

• Published in: Doklady. Biochemistry and biophysics 2023-02, Vol.508 (1), p.6-11
• Main Authors: Zakharenko, A. L., Malakhova, A. A., Dyrkheeva, N. S., Okorokova, L. S., Medvedev, S. P., Zakian, S. M., Kabilov, M. R., Tupikin, A. A., Lavrik, O. I.
• Format: Article
• Language: English
• Subjects: Base excision repair; Biochemistry; Biochemistry, Biophysics, and Molecular Biology; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Deoxyribonucleic acid; DNA; DNA glycosylase; DNA Glycosylases - genetics; DNA Glycosylases - metabolism; DNA Repair; DNA-directed DNA polymerase; Gene expression; Gene Knockout Techniques; Genes; HEK293 Cells; Humans; Life Sciences; Molecular Biology; Poly (ADP-Ribose) Polymerase-1 - genetics; Poly (ADP-Ribose) Polymerase-1 - metabolism; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerases - genetics; Proteasomes; Proteins
• ISSN: 1607-6729; 1608-3091
• DOI: 10.1134/S1607672922700028

The effect of PARP1 knockout in HEK293 cells on the gene expression of DNA base excision repair (BER) proteins was studied. It was shown that the expression of all differentially expressed genes (DEGs) of BER was reduced by knockout. The expression of the DNA glycosylase gene NEIL1 , which is considered to be one of the common “hubs” for binding BER proteins, has changed the most. The expression of genes of auxiliary subunits of DNA polymerases δ and ε is also significantly reduced. The PARP1 gene knockout cell line obtained is an adequate cell model for studying the activity of the BER process in the absence of PARP1 and testing drugs aimed at inhibiting repair processes. It has been found for the first time that knockout of the PARP1 gene results in a significant change in the level of expression of proteins responsible for ribosome biogenesis and the functioning of the proteasome.