From the Nuclear Pore to the Fibrous Corona: A MAD Journey to Preserve Genome Stability.,BioEssays

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From the Nuclear Pore to the Fibrous Corona: A MAD Journey to Preserve Genome Stability.
BioEssays ( IF 3.2 ) Pub Date : 2020-09-03 , DOI: 10.1002/bies.202000132
Sofia Cunha-Silva _{1,

2,

3} , Carlos Conde _{1,

2}

Affiliation

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.

中文翻译：

从核孔到纤维冠：保持基因组稳定性的疯狂之旅。

动粒与核孔复合物 (NPC) 之间的关系密切但知之甚少。几个 NPC 成分和相关蛋白质被重新定位到有丝分裂的动粒，以协助不同的活动，确保忠实的染色体分离。Mad1-c-Mad2 复合体就是这种情况，它是纺锤体组装检查点 (SAC) 的催化核心，这是一种延迟后期直到所有动粒都附着在纺锤体微管上的监视途径。Mad1-c-Mad2 被招募到未连接的动粒的离散域中，从那里它促进后期抑制复合物组装中的限速步骤。SAC 熟练程度进一步要求 Mad1-c-Mad2 在相间期间锚定在 NPC 上。然而，这种安排与 SAC 功能的机械相关性仍然不明确。最近的研究揭示了协调从 NPC 释放 Mad1-c-Mad2 与其迅速募集到动粒的分子基础。在这里，回顾了有关 Mad1-c-Mad2 功能和时空调节的当前知识，并强调了仍未解决的关键问题。

更新日期：2020-10-22

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