Multiple Duties for Spindle Assembly Checkpoint Kinases in Meiosis

Abstract

Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. In mitosis, the spindle assembly checkpoint (SAC) controls the proper attachment to and alignment of chromosomes on the spindle. The SAC detects errors and induces a cell cycle arrest in metaphase, preventing chromatid separation. Once all chromosomes are properly attached, the SAC-dependent arrest is relieved and chromatids separate evenly into daughter cells. The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. In meiosis, haploid cells containing new genetic combinations are generated from a diploid cell through two specialized cell divisions. Though apparently less robust, SAC control also exists in meiosis. Recently, it has emerged that SAC kinases have additional roles in executing accurate chromosome segregation during the meiotic divisions. Here, we summarize the main differences between mitotic and meiotic cell divisions, and explain why meiotic divisions pose special challenges for correct chromosome segregation. The less-known meiotic roles of the SAC kinases are described, with a focus on two model systems: yeast and mouse oocytes. The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3), and Aurora B and C (Ipl1) will be discussed. Insights into the molecular signaling pathways that bring about the special chromosome segregation pattern during meiosis will help us understand why human oocytes are so frequently aneuploid.

Structural and functional characterization of the Spo11 core complex

“…In vivo, these mutations caused reduced and delayed DSB formation as assessed by labeling of Spo11-oligo complexes ( Figure 6B) and direct DSB measurements at the CCT6 hotspot ( Supplementary Figure 8A, B). Meiotic divisions were also delayed (Supplementary Figure 8C), possibly because frequently achiasmate chromosomes trigger the spindle checkpoint (Marston and Wassmann, 2017).…”

Peer Review #1 of "OLA1 is responsible for normal spindle assembly and SAC activation in mouse oocytes (v0.1)"

“…Manuscript to be reviewed activates the APC/C activity to accelerate SECURIN degradation and anaphase I onset (Marston et al, 2017 ). Defects in SAC function can result in incorrect attachments of chromosome with microtubules, and leads to missegregation (Miao et al, 2017;Lu et al, 2017;Li et al, 2009).…”

The proteomic landscape of centromeric chromatin reveals an essential role for the Ctf19CCANcomplex in meiotic kinetochore assembly

“…Kinetochores promote pericentromeric cohesin enrichment through cohesin loading onto centromeres (Eckert et al, 2007;Fernius and Marston, 2009;Fernius et al, 2013;Ng et al, 2009), shape pericentromere structure (Paldi et al, 2020), and monitor proper attachment of chromosomes to microtubules (Foley and Kapoor, 2013;Marston and Wassmann, 2017). They also adopt additional roles during meiosis, including non-homologous centromere coupling and repression of meiotic recombination in prophase (Kuhl and Vader, 2019;Kurdzo and Dawson, 2015;Vincenten et al, 2015).…”