Laboratoire interdisciplinaire de Physique, Université Joseph Fourier (Grenoble 1), Domaine universitaire, Bat. E45 140, Rue de la physique, BP 87, 38402, Saint Martin d'Hères, Cedex 9, France.
Chromosome Instability & Dynamics Laboratory, Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal.
Nat Commun. 2019 Jan 3;10(1):52. doi: 10.1038/s41467-018-07965-6.
The presence of aberrant number of centrioles is a recognized cause of aneuploidy and hallmark of cancer. Hence, centriole duplication needs to be tightly regulated. It has been proposed that centriole separation limits centrosome duplication. The mechanism driving centriole separation is poorly understood and little is known on how this is linked to centriole duplication. Here, we propose that actin-generated forces regulate centriole separation. By imposing geometric constraints via micropatterns, we were able to prove that precise acto-myosin force arrangements control direction, distance and time of centriole separation. Accordingly, inhibition of acto-myosin contractility impairs centriole separation. Alongside, we observed that organization of acto-myosin force modulates specifically the length of S-G2 phases of the cell cycle, PLK4 recruitment at the centrosome and centriole fidelity. These discoveries led us to suggest that acto-myosin forces might act in fundamental mechanisms of aneuploidy prevention.
中心体数量异常是导致非整倍体和癌症的公认原因。因此，中心体复制需要受到严格调控。有人提出，中心体分离限制了中心体的复制。然而，驱动中心体分离的机制还不太清楚，也不太清楚这与中心体复制是如何联系在一起的。在这里，我们提出肌动蛋白产生的力调节中心体分离。通过微图案施加几何约束，我们能够证明精确的肌动球蛋白力排列控制着中心体分离的方向、距离和时间。因此，肌动球蛋白收缩的抑制会损害中心体分离。同时，我们观察到肌动球蛋白力的组织特别调节细胞周期的 S-G2 期的长度、中心体处 PLK4 的募集和中心体保真度。这些发现使我们提出肌动球蛋白力可能在预防非整倍体的基本机制中发挥作用。
