Abstract
Faithful chromosome segregation during mitosis is crucial for maintaining genome stability. The spindle assembly checkpoint (SAC) is a surveillance mechanism that ensures accurate mitotic progression. Defective SAC signaling leads to premature sister chromatid separation and aneuploid daughter cells. Mechanistically, the SAC couples the kinetochore microtubule attachment status to the cell cycle progression machinery. In the presence of abnormal kinetochore microtubule attachments, the SAC prevents the metaphase-to-anaphase transition through a complex kinase-phosphatase signaling cascade which results in the correct balance of SAC components recruited to the kinetochore. The correct kinetochore localization of SAC proteins is a prerequisite for robust SAC signaling and, hence, accurate chromosome segregation. Here, we review recent progresses on the kinetochore recruitment of core SAC factors.
Highlights
During cell division, it is crucial to transmit the duplicated genome to two daughter cells .Kinetochores, the large protein complexes that assemble at the centromere of a chromosome, are an essential protein machinery that orchestrates faithful mitosis
Monopolar spindle 1 (Mps1) phosphorylates the outer kinetochore protein Kinetochore null 1 (Knl1) at several Met-Glu-Leu-Thr (MELT) motifs, creating docking sites for the recruitment and formation of the mitotic checkpoint complex (MCC) which consists of mitotic arrest deficient 2 (Mad2), budding uninhibited by benzimidazoles related 1 (BubR1), budding uninhibited by benzimidazole 3 (Bub3) and cell division cycle 20 (Cdc20) [3,8,9,10]
This study suggests the existence of a remarkable phosphorylation-regulated plasticity in the inner–outer kinetochore interface during different mitotic stages and in different species/cells
Summary
It is crucial to transmit the duplicated genome to two daughter cells . The checkpoint kinase Monopolar spindle 1 (Mps1) phosphorylates its substrates to activate the SAC [3], while Aurora B kinase, the catalytic subunit of chromosome passenger complex (CPC), phosphorylates the targets at improperly attached kinetochores to promote error correction [4]. Mps phosphorylates the outer kinetochore protein Kinetochore null 1 (Knl1) at several Met-Glu-Leu-Thr (MELT) motifs, creating docking sites for the recruitment and formation of the MCC which consists of mitotic arrest deficient 2 (Mad2), budding uninhibited by benzimidazoles related 1 (BubR1), budding uninhibited by benzimidazole 3 (Bub3) and cell division cycle 20 (Cdc20) [3,8,9,10]. Mps from its downstream substrates, effectively terminating SAC signaling [33] Another example is chromosome-bound Bub that it is hyperphosphorylated and activated at unattached kinetochores [34]. We will review the molecular pathways of kinetochore recruitment of these core SAC proteins
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