SAC during early cell divisions: Sacrificing fidelity over timely division, regulated differently across organisms

Abstract

Early embryogenesis is marked by a frail Spindle Assembly Checkpoint (SAC). The time of SAC acquisition varies depending on the species, cell size or a yet to be uncovered developmental timer. This means that for a specific number of divisions, biorientation of sister chromatids occurs unsupervised. When error‐prone segregation is an issue, an aneuploidy‐selective apoptosis system can come into play to eliminate chromosomally unbalanced cells resulting in healthy newborns. However, aneuploidy content can be too great to overcome, endangering viability. SAC generates a diffusible signal to lengthen time spent in mitosis if needed, ensuring correct chromosome segregation, a fundamental factor in the generation of euploid cells. Thus, it remains puzzling what benefit could come from delaying SAC acquisition till later in the development. In this review, we describe what is known on SAC acquisition in distinct species and highlight pending research as well as potential applications for such knowledge.

Upregulation of TTK expression is associated with poor prognosis and immune infiltration in endometrial cancer patients

“…TTK plays a key role in safeguarding chromosome segregation fidelity, participating in the assembly of mitotic checkpoint complexes, regulating cytokinesis, responding to DNA damage, and promoting accurate chromosome alignment [ 9 ]. The spindle assembly checkpoint (SAC) represents the primary mechanism for preserving chromosomal stability during cytokinesis [ 10 ]. The SAC pathway, involving TTK, Polo, Aurora, Bub, BubR and Mad, detects misoriented chromosomes, establishes proper bipolar connections with the spindle, and diminishes chromosomal mismatch errors prior to late-stage initiation [ 8 ].…”

Nuclear-enriched protein phosphatase 4 ensures outer kinetochore assembly prior to nuclear dissolution

“…Bi-orientation is accompanied by chromosome alignment at the spindle equator, and a mitotic checkpoint ensures all chromosomes have time to bi-orient before sister chromatids separate in anaphase ( Lara-Gonzalez et al, 2021 ). Efficient bi-orientation and alignment of chromosomes are crucial in the rapidly dividing cells of the early embryo, which lack a robust checkpoint response ( Duro and Nilsson, 2020 ).…”

Nuclear-enriched protein phosphatase 4 ensures outer kinetochore assembly prior to nuclear dissolution

“…Efficient bi-orientation and alignment of chromosomes is crucial in the rapidly dividing cells of the early embryo, which lack a robust checkpoint response (Duro and Nilsson, 2020).…”

“…Bi-orientation is accompanied by chromosome alignment at the spindle equator, and a mitotic checkpoint ensures all chromosomes have time to bi-orient before sister chromatids separate in anaphase (Lara-Gonzalez et al ., 2021). Efficient bi-orientation and alignment of chromosomes is crucial in the rapidly dividing cells of the early embryo, which lack a robust checkpoint response (Duro and Nilsson, 2020).…”