Institute of Molecular Biology gGmbH (IMB), Ackermannweg 4, D - 55128, Mainz, Germany.
Mainz Biomed N.V., Robert-Koch-Str. 50, D - 55129, Mainz, Germany.
Nat Commun. 2023 Jun 24;14(1):3787. doi: 10.1038/s41467-023-39517-y.
The actin cytoskeleton is of fundamental importance for cellular structure and plasticity. However, abundance and function of filamentous actin in the nucleus are still controversial. Here we show that the actin-based molecular motor myosin VI contributes to the stabilization of stalled or reversed replication forks. In response to DNA replication stress, myosin VI associates with stalled replication intermediates and cooperates with the AAA ATPase Werner helicase interacting protein 1 (WRNIP1) in protecting these structures from DNA2-mediated nucleolytic attack. Using functionalized affinity probes to manipulate myosin VI levels in a compartment-specific manner, we provide evidence for the direct involvement of myosin VI in the nucleus and against a contribution of the abundant cytoplasmic pool during the replication stress response.
肌动蛋白细胞骨架对于细胞结构和可塑性至关重要。然而，核内丝状肌动蛋白的丰度和功能仍存在争议。在这里，我们发现肌球蛋白 VI 这一基于肌动蛋白的分子马达有助于稳定停滞或反转的复制叉。在应对 DNA 复制应激时，肌球蛋白 VI 与停滞的复制中间体结合，并与 AAA ATP 酶 Werner 解旋酶相互作用蛋白 1（WRNIP1）合作，保护这些结构免受 DNA2 介导的核酶攻击。我们使用功能化的亲和探针以特定于隔室的方式操纵肌球蛋白 VI 的水平，为肌球蛋白 VI 直接参与核内过程提供了证据，同时排除了丰富的细胞质池在复制应激反应中的作用。
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