i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, 4200-135, Portugal.
IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, 4200-135, Portugal.
Bioessays. 2020 Nov;42(11):e2000132. doi: 10.1002/bies.202000132. Epub 2020 Sep 3.
The relationship between kinetochores and nuclear pore complexes (NPCs) is intimate but poorly understood. Several NPC components and associated proteins are relocated to mitotic kinetochores to assist in different activities that ensure faithful chromosome segregation. Such is the case of the Mad1-c-Mad2 complex, the catalytic core of the spindle assembly checkpoint (SAC), a surveillance pathway that delays anaphase until all kinetochores are attached to spindle microtubules. Mad1-c-Mad2 is recruited to discrete domains of unattached kinetochores from where it promotes the rate-limiting step in the assembly of anaphase-inhibitory complexes. SAC proficiency further requires Mad1-c-Mad2 to be anchored at NPCs during interphase. However, the mechanistic relevance of this arrangement for SAC function remains ill-defined. Recent studies uncover the molecular underpinnings that coordinate the release of Mad1-c-Mad2 from NPCs with its prompt recruitment to kinetochores. Here, current knowledge on Mad1-c-Mad2 function and spatiotemporal regulation is reviewed and the critical questions that remain unanswered are highlighted.
着丝粒与核孔复合物（NPC）之间的关系密切，但知之甚少。一些 NPC 成分和相关蛋白被重新定位到有丝分裂的着丝粒上，以协助确保染色体正确分离的不同活动。Mad1-c-Mad2 复合物就是这种情况，Mad1-c-Mad2 复合物是纺锤体组装检查点（SAC）的催化核心，是一种监测途径，它会延迟后期，直到所有的着丝粒都与纺锤体微管相连。Mad1-c-Mad2 从未附着的着丝粒的离散区域招募，在那里它促进了抑制复合物组装的限速步骤。SAC 的效率还需要 Mad1-c-Mad2 在间期锚定在 NPC 上。然而，这种安排对 SAC 功能的机械相关性仍然定义不明确。最近的研究揭示了协调 Mad1-c-Mad2 从 NPC 释放及其迅速招募到着丝粒的分子基础。在这里，回顾了 Mad1-c-Mad2 功能和时空调节的现有知识，并强调了仍然存在的关键问题。
