NUCKS1 (nuclear ubiquitous casein kinase and cyclin-dependent kinase substrate 1) is a chromatin-associated, vertebrate-specific, and multifunctional protein with a role in DNA damage signaling and repair. Previously, we have shown that NUCKS1 helps maintain homologous recombination (HR) DNA repair in human cells and functions as a tumor suppressor in mice. However, the mechanisms by which NUCKS1 positively impacts these processes had remained unclear. Here, we show that NUCKS1 physically and functionally interacts with the DNA motor protein RAD54. Upon exposure of human cells to DNA-damaging agents, NUCKS1 controls the resolution of RAD54 foci. In unperturbed cells, NUCKS1 prevents RAD54’s inappropriate engagement with RAD51AP1. In vitro, NUCKS1 stimulates the ATPase activity of RAD54 and the RAD51–RAD54-mediated strand invasion step during displacement loop formation. Taken together, our data demonstrate that the NUCKS1 protein is an important new regulator of the spatiotemporal events in HR.

中文翻译：

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NUCKS1在同源重组DNA修复中促进RAD54活性

NUCKS1（核普遍存在酪蛋白激酶和细胞周期蛋白依赖性激酶底物 1）是一种染色质相关、脊椎动物特异性、多功能蛋白，在 DNA 损伤信号转导和修复中发挥作用。此前，我们已经证明 NUCKS1 有助于维持人类细胞中的同源重组 (HR) DNA 修复，并在小鼠中发挥肿瘤抑制因子的作用。然而，NUCKS1 对这些过程产生积极影响的机制仍不清楚。在这里，我们展示了 NUCKS1 在物理和功能上与 DNA 马达蛋白 RAD54 相互作用。当人类细胞暴露于 DNA 损伤剂时，NUCKS1 控制 RAD54 焦点的分辨率。在未受干扰的细胞中，NUCKS1 可以防止 RAD54 与 RAD51AP1 的不当结合。在体外，NUCKS1 刺激 RAD54 的 ATP 酶活性以及置换环形成过程中 RAD51-RAD54 介导的链侵入步骤。综上所述，我们的数据表明 NUCKS1 蛋白是 HR 时空事件的重要新调节因子。