α-Actinin-4-Dependent Regulation of DNA Break Repair Is Not Dependent on NF-kB Activity

Abstract: α-Actinin-4 is an actin-binding protein involved in a wide range of cellular processes. Along with actin and other proteins of the actin cytoskeleton, α-actinin-4 is found not only in the cytoplasm, but also in the nucleus of various types of cells. As a nuclear protein, it takes part in regulating the activity of some transcription factors. In particular, it can regulate the activity of the NF-kB factor, which largely determines the resistance of cancer cells to apoptosis and anticancer therapy. Our previous studies revealed that α-actinin-4 can influence the resistance of cancer cells to topoisomerase II inhibitors and determine the efficiency of DNA double-strand break repair by regulating the assembly of HRR and NHEJ protein complexes. In this work, we tried to answer the question of how α-actinin-4 is involved in the regulation of the double-stranded DNA breaks repair under genotoxic stress. Our results indicate that the effect of α-actinin-4 on the repair process in H1299 non-small-cell lung-cancer cells does not depend on the activity of the transcription factor NF-kB. We found that, in the nucleus of H1299 cells, α-actinin-4 is localized not only in the nucleoplasm, but also shows close association with chromatin. © Pleiades Publishing, Ltd. 2024. ISSN 1990-519X, Cell and Tissue Biology, 2024, Vol. 18, No. 3, pp. 314–323. Pleiades Publishing, Ltd., 2024. Russian Text The Author(s), 2024, published in Tsitologiya, 2024, Vol. 66, No. 1, pp. 35–45.