Biochimie, volume 199, pages 139-149
Transcriptome analysis of HEK 293T cells revealed different significance of the depletion of DNA-dependent protein kinase subunits, Ku70, Ku80, and DNA-PKcs
Publication type: Journal Article
Publication date: 2022-08-01
Biochemistry
General Medicine
Abstract
DNA-dependent protein kinase (DNA-PK) is a key player in the NHEJ repair pathway. DNA-PK and its subunits, Ku70, Ku80, and catalytic subunit (DNA-PKcs), also participate in other cellular processes; however, there are still no systemic data on the effect of depletion of Ku70, Ku80 and DNA-PKcs on cell functions in the same cell line. Here, we analyzed transcriptome changes in HEK 293T cells after depletion of each DNA-PK subunit. Depletion of various DNA-PK subunits resulted in dramatic differences in the number of differentially expressed genes: only 7 genes changed more than 2-fold in DNA-PKcs-deficient cells, 29 genes in Ku80-deficient, 219 genes in Ku70-deficient. All DNA-PKcs-dependent genes were stress-related and depended on both Ku70 and Ku80. Two-thirds of Ku80-dependent genes were also differentially expressed in the Ku70-deficient line. Most Ku70-dependent genes were altered exclusively in Ku70-depleted cells, indicating that Ku70 is involved in the regulation of more processes than Ku80. GO enrichment analysis showed the effect of Ku70 knockdown on cell adhesion and matrix organization, protein degradation, cell proliferation, and differentiation. Depletion of Ku70, but not Ku80, provided greater cell motility and disassembly of cell-cell contacts. These data clearly indicate that Ku70 is more functionally important for the cell life than DNA-PKcs and even Ku80.
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Shadrina O. et al. Transcriptome analysis of HEK 293T cells revealed different significance of the depletion of DNA-dependent protein kinase subunits, Ku70, Ku80, and DNA-PKcs // Biochimie. 2022. Vol. 199. pp. 139-149.
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Shadrina O., Garanina I., Anisenko A., Kireev I., Gottikh M. B. Transcriptome analysis of HEK 293T cells revealed different significance of the depletion of DNA-dependent protein kinase subunits, Ku70, Ku80, and DNA-PKcs // Biochimie. 2022. Vol. 199. pp. 139-149.
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TY - JOUR
DO - 10.1016/j.biochi.2022.04.004
UR - https://doi.org/10.1016%2Fj.biochi.2022.04.004
TI - Transcriptome analysis of HEK 293T cells revealed different significance of the depletion of DNA-dependent protein kinase subunits, Ku70, Ku80, and DNA-PKcs
T2 - Biochimie
AU - Shadrina, Olga
AU - Garanina, Irina
AU - Anisenko, Andrey
AU - Kireev, I.
AU - Gottikh, Marina B.
PY - 2022
DA - 2022/08/01 00:00:00
PB - Elsevier
SP - 139-149
VL - 199
SN - 0300-9084
SN - 6183-1638
ER -
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@article{2022_Shadrina,
author = {Olga Shadrina and Irina Garanina and Andrey Anisenko and I. Kireev and Marina B. Gottikh},
title = {Transcriptome analysis of HEK 293T cells revealed different significance of the depletion of DNA-dependent protein kinase subunits, Ku70, Ku80, and DNA-PKcs},
journal = {Biochimie},
year = {2022},
volume = {199},
publisher = {Elsevier},
month = {aug},
url = {https://doi.org/10.1016%2Fj.biochi.2022.04.004},
pages = {139--149},
doi = {10.1016/j.biochi.2022.04.004}
}