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Transcriptomic analysis of HEK293A cells with a CRISPR/Cas9-mediated TDP1 knockout.

Authors :
Dyrkheeva NS
Zakharenko AL
Malakhova AA
Okorokova LS
Shtokalo DN
Medvedev SP
Tupikin AA
Kabilov MR
Lavrik OI
Source :
Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2024 Jul; Vol. 1868 (7), pp. 130616. Date of Electronic Publication: 2024 Apr 14.
Publication Year :
2024

Abstract

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a human DNA repair protein. It is a member of the phospholipase D family based on structural similarity. TDP1 is a key enzyme of the repair of stalled topoisomerase 1 (TOP1)-DNA complexes. Previously, with the CRISPR/Cas9 method, we obtained HEK293A cells with a homozygous knockout of the TDP1 gene and used the TDP1 knockout cells as a cellular model for studying mechanisms of action of an anticancer therapy. In the present work, we hypothesized that the TDP1 knockout would alter the expression of DNA repair-related genes. By transcriptomic analysis, we investigated for the first time the effect of the TDP1 gene knockout on genes' expression changes in the human HEK293A cell line. We obtained original data implying a role of TDP1 in other processes besides the repair of the DNA-TOP1 complex. Differentially expressed gene analysis revealed that TDP1 may participate in cell adhesion and communication, spermatogenesis, mitochondrial function, neurodegeneration, a cytokine response, and the MAPK signaling pathway.<br />Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest with the contents of this article.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1872-8006
Volume :
1868
Issue :
7
Database :
MEDLINE
Journal :
Biochimica et biophysica acta. General subjects
Publication Type :
Academic Journal
Accession number :
38621596
Full Text :
https://doi.org/10.1016/j.bbagen.2024.130616