Forces generated by molecular motors and the cytoskeleton move the nucleus and genome during many cellular processes, including cell migration and division. How these forces impact the genome, and whether cells regulate cytoskeletal forces to preserve genome integrity is unclear. We recently demonstrated that, in budding yeast, mutants that stabilize the microtubule cytoskeleton cause excessive movement of the mitotic spindle and nucleus. We found that increased nuclear movement results in DNA damage and increased time to repair the damage through homology-directed repair. Our results indicate that nuclear movement impairs DNA repair through increased tension on chromosomes and nuclear deformation. However, the previous studies have shown genome mobility, driven by cytoskeleton-based forces, aids in homology-directed DNA repair. This sets up an apparent paradox, where genome mobility may prevent or promote DNA repair. Hence, this review explores how the genome is affected by nuclear movement and how genome mobility could aid or hinder homology-directed repair.

中文翻译：

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帮助或阻碍：基于微管的作用力如何导致基因组损伤和修复？

在许多细胞过程中，包括细胞迁移和分裂，分子马达和细胞骨架产生的力使细胞核和基因组移动。这些力如何影响基因组，以及细胞是否调节细胞骨架力以保持基因组完整性尚不清楚。我们最近证明，在发芽的酵母中，稳定微管细胞骨架的突变体导致有丝分裂纺锤体和核的过度运动。我们发现增加的核运动导致DNA损伤，并通过同源性指导的修复来修复损伤的时间增加。我们的结果表明，核运动通过增加染色体上的张力和核变形而损害DNA修复。但是，以前的研究表明，由基于细胞骨架的力驱动的基因组迁移有助于同源性指导的DNA修复。这建立了一个明显的悖论，即基因组迁移可能阻止或促进DNA修复。因此，本综述探讨了核运动如何影响基因组以及基因组的移动性如何帮助或阻碍同源性指导的修复。