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

Q4 Biochemistry, Genetics and Molecular Biology Cell and Tissue Biology Pub Date : 2024-06-03 DOI:10.1134/s1990519x24700251
D. V. Krieger, G. V. Vasilyeva, E. V. Lomert, D. G. Tentler
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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.

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α-Actinin-4对DNA断裂修复的调控不依赖于NF-kB的活性
摘要 α-肌动蛋白-4是一种肌动蛋白结合蛋白,参与多种细胞过程。α-Actinin-4与肌动蛋白和其他肌动蛋白细胞骨架蛋白一起,不仅存在于细胞质中,还存在于各种细胞的细胞核中。作为一种核蛋白,它参与调节一些转录因子的活性。特别是,它可以调节 NF-kB 因子的活性,而 NF-kB 因子在很大程度上决定了癌细胞对凋亡和抗癌治疗的抵抗力。我们之前的研究发现,α-actinin-4 可以影响癌细胞对拓扑异构酶 II 抑制剂的耐受性,并通过调节 HRR 和 NHEJ 蛋白复合物的组装来决定 DNA 双链断裂修复的效率。在这项工作中,我们试图回答α-actinin-4如何参与调控基因毒性应激下的DNA双链断裂修复这一问题。我们的研究结果表明,α-actinin-4 对 H1299 非小细胞肺癌细胞修复过程的影响并不依赖于转录因子 NF-kB 的活性。我们发现,在 H1299 细胞的细胞核中,α-actinin-4 不仅定位于核质,而且还与染色质密切相关。
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来源期刊
Cell and Tissue Biology
Cell and Tissue Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
0.80
自引率
0.00%
发文量
51
期刊介绍: The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.
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