The Role of MAP Kinases in the Induced Histone H2AX Phosphorylation in Transformed Cells

O. O. Gnedina; Гнедина О. О.; A. V. Morshneva; Моршнева А. В.; M. V. Igotti; Иготти М. В.

doi:10.31857/S0041377123010030

The Role of MAP Kinases in the Induced Histone H2AX Phosphorylation in Transformed Cells

Authors: Gnedina O.O.¹, Morshneva A.V.¹, Igotti M.V.¹
Affiliations:
1. Institute of Cytology, Russian Academy of Sciences
Issue: Vol 65, No 1 (2023)
Pages: 54-63
Section: Articles
URL: https://journals.rcsi.science/0041-3771/article/view/140067
DOI: https://doi.org/10.31857/S0041377123010030
EDN: https://elibrary.ru/GOTCEB
ID: 140067

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Abstract
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Abstract

Previously, we have shown that inhibitors of histone deacetylases (HDIs) do not induce DNA double strand breaks (DNA DSBs). However, like genotoxic agents, HDIs initiate the accumulation of phosphorylated histone H2AX (γH2AX), which is a DNA DSB marker. HDIs can also reduce the efficiency of repair of DNA damaged by genotoxic effects in transformed cells. The aim of this work was to identify the signaling pathways leading to the accumulation of γH2AX under the HDIs treatment in transformed cells. There was considered the role of the MAPK family kinases in phosphorylation of histone H2AX as well as inhibition of DNA repair induced with HDI sodium butyrate (NaBut). It was shown that the accumulation of γH2AX under the NaBut treatment is accompanied by a decrease of the ERK and PKB/Akt kinases phosphorylation level in transformed cells. The activating phosphorylation of p38 kinase increases under the NaBut treatment, causing Wip1 phosphatase accumulation, which may be one of the reasons for the DNA repair inhibition. Suppression of p38 kinase activity abolishes the NaBut-induced inhibition of repair efficiency. The data obtained suggest the role of the p38/Wip1 pathway in the HDIs-induced decrease in repair efficiency in transformed cells.

Keywords

HDAC inhibitor, sodium butyrate, histone H2AX phosphorylation, MAP kinase, DNA repair, Wip1 phosphatase

References

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