The spindle assembly checkpoint promotes chromosome bi-orientation: A novel Mad1 role in chromosome alignment

Abstract

Faithful chromosome segregation relies on dynamic interactions between spindle microtubules and chromosomes. Especially, all chromosomes must be aligned at the equator of the spindle to establish biorientation before they start to segregate. The spindle assembly checkpoint (SAC) monitors this process, inhibiting chromosome segregation until all chromosomes achieve bi-orientation. The original concept of 'checkpoints' was proposed as an external surveillance system that does not play an active role in the process it monitors. However, accumulating evidence from recent studies suggests that SAC components do play an active role in chromosome bi-orientation. In this review, we highlight a novel Mad1 role in chromosome alignment, which is the first conserved mechanism that links the SAC and kinesin-mediated chromosome gliding.

Kinesin-5 Is Dispensable for Bipolar Spindle Formation and Elongation in Candida albicans, but Simultaneous Loss of Kinesin-14 Activity Is Lethal

“…To determine whether midzone clustering of Ca Kip1 requires overlapping arrays of antiparallel ipMTs in this region, we imaged Ca Kip1-GFP in fields of unsynchronized cells lacking kinesin-14 activity ( cik1 Δ/Δ). In other yeasts, kinesin-14 is important for organizing antiparallel ipMT interactions in the midzone so that kinesin-5 motors can properly cross-link and slide antiparallel spindle MTs (39, 40, 50). Without kinesin-14 activity, Ca Kip1 remains exclusively near the poles of bipolar spindles and one pole of dissociated half-spindles, presumably due to paucity of antiparallel ipMT overlaps (Fig.…”

Crossover Interference, Crossover Maturation, and Human Aneuploidy

“…Moreover, the unusual CO patterns predicted to result from CMI closely match and/or can readily explain the unusual patterns that are associated with aneuploidy. [1,[66][67][68][69][70][71] Aneuploidy is also associated with the occurrence of COs very close to the centromere. [65] It remains to be determined exactly why certain CO configurations are prone to mis-segregation.…”

“…Many configurations of COs (and thus chiasmata) that are prone to mis-segregation may set up only a reduced level of tension, e.g., if all COs are too far from the centromere or are present on only one chromosome arm, either in an acrocentric chromosome or due to subtraction of all COs from one arm of a metacentric chromosome. [1,[66][67][68][69][70][71] Aneuploidy is also associated with the occurrence of COs very close to the centromere. [72] CMI is not predicted to increase this configuration, which might exert its effects by disrupting the centromere function.…”

Loss of Kif18A Results in Spindle Assembly Checkpoint Activation at Microtubule-Attached Kinetochores

“…Cdc20 is an essential co-factor of the multi-subunit E3 ligase anaphase-promoting complex/cyclosome (APC/C), and incorporation of Cdc20 in the MCC renders it incapable of activating the APC/C [8], thereby preventing premature chromatid separation [9]. SAC inactivation occurs when correct kinetochore-microtubule (k-Mt) attachments displace the various checkpoint proteins from the kinetochore, so that MCC production will cease and Cdc20 can activate the APC/C [3,10,11], resulting in anaphase onset.…”