The Arp2/3 inhibitory protein Arpin inhibits homology-directed DNA repair

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Biology of the Cell Pub Date : 2024-08-09 DOI:10.1111/boc.202400073

Gleb Simanov, Nathalie Rocques, Stéphane Romero, Leanne de Koning, Sophie Vacher, Thierry Dubois, Ivan Bièche, Alexis M. Gautreau

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引用次数: 0

Abstract

Background information

Arpin, an Arp2/3 inhibitory protein, inhibits lamellipodial protrusions and cell migration. Arpin expression is lost in tumor cells of several cancer types.

Results

Here we analyzed expression levels of Arpin and various markers using Reverse Phase Protein Array (RPPA) in human mammary carcinomas. We found that Arpin protein levels were correlated with those of several DNA damage response markers. Arpin-null cells display enhanced clustering of double stand breaks (DSBs) when cells are treated with a DNA damaging agent, in line with a previously described role of the Arp2/3 complex in promoting DSB clustering for homologous DNA repair (HDR) in the nucleus. Using a specific HDR assay, we further showed that Arpin depletion increased HDR efficiency two-fold through its ability to inactivate the Arp2/3 complex.

Conclusions

Arpin regulates both cell migration in the cytosol and HDR in the nucleus.

Significance

Loss of Arpin expression coordinates enhanced cell migration with up-regulated DNA repair, which is required when DNA damage is induced by active cell migration.

Abstract Image

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Arp2/3 抑制蛋白 Arpin 可抑制同源 DNA 修复。

背景信息Arpin是一种Arp2/3抑制蛋白，可抑制薄片突起和细胞迁移。Arpin 在几种癌症类型的肿瘤细胞中表达丢失：在此，我们使用反相蛋白质阵列（RPPA）分析了 Arpin 和各种标记物在人类乳腺癌中的表达水平。我们发现，Arpin 蛋白水平与几种 DNA 损伤反应标记物的水平相关。当细胞受到DNA损伤剂处理时，Arpin缺失细胞显示出更强的双支架断裂（DSB）集群，这与之前描述的Arp2/3复合物在促进细胞核内同源DNA修复（HDR）的DSB集群中的作用一致。我们使用一种特异性 HDR 试验进一步表明，通过使 Arp2/3 复合物失活，Arpin 的耗竭使 HDR 效率提高了两倍：Arpin同时调节细胞在细胞质中的迁移和细胞核中的HDR：意义：Arpin表达的缺失可协调细胞迁移的增强和DNA修复的上调，当DNA损伤由活跃的细胞迁移诱导时，DNA修复是必需的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology of the Cell 生物-细胞生物学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.