Transcriptome analysis of HEK 293T cells revealed different significance of the depletion of DNA-dependent protein kinase subunits, Ku70, Ku80, and DNA-PKcs

Shadrina, O.; Garanina, I.; Anisenko, A.; Kireev, I.; Gottikh, M.

Авторы: Shadrina Olga, Garanina Irina, Anisenko Andrey, Kireev Igor, Gottikh Marina
Журнал: Biochimie
Том: 199
Год издания: 2022
Издательство: Elsevier BV
Местоположение издательства: Netherlands
Первая страница: 139
Последняя страница: 149
DOI: 10.1016/j.biochi.2022.04.004
Аннотация: DNA-dependent protein kinase (DNA-PK) is a key player in the NHEJ repair pathway. DNAPK and its subunits, Ku70, Ku80, and catalytic subunit (DNA-PKcs), also participate in other cellularprocesses; however, there are still no systemic data on the effect of depletion of Ku70, Ku80 and DNAPKcs on cell functions in the same cell line. Here, we analyzed transcriptome changes in HEK 293Tcells after depletion of each DNA-PK subunit. Depletion of various DNA-PK subunits resulted indramatic differences in the number of differentially expressed genes: only 7 genes changed more than2-fold in DNA-PKcs-deficient cells, 29 genes in Ku80-deficient, 219 genes in Ku70-deficient. AllDNA-PKcs-dependent genes were stress-related and depended on both Ku70 and Ku80. Two-thirdsof 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 inthe regulation of more processes than Ku80. GO enrichment analysis showed the effect of Ku70knockdown on cell adhesion and matrix organization, protein degradation, cell proliferation, anddifferentiation. Depletion of Ku70, but not Ku80, provided greater cell motility and disassembly ofcell-cell contacts. These data clearly indicate that Ku70 is more functionally important for the cell life than DNA-PKcs and even Ku80.
Добавил в систему: Готтих Марина Борисовна

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Transcriptome analysis of HEK 293T cells revealed different significance of the depletion of DNA-dependent protein kinase subunits, Ku70, Ku80, and DNA-PKcsстатья

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