Kinetochore structure and function.
The vertebrate kinetochore is a complex structure that specifies the attachments between the chromosomes and microtubules of the spindle and is thus essential for accurate chromosome segregation. Kinetochores are assembled on centromeric chromatin through complex pathways that are coordinated with the cell cycle. In the light of recent discoveries on how proteins assemble onto kinetochores and interact with each other, we review these findings in this article (which is part of the Chromosome Segregation and Aneuploidy series), and discuss their implications for the current mitotic checkpoint models - the template model and the two-step model. The template model proposes that Mad1-Mad2 at kinetochores acts as a template to change the conformation of another binding molecule of Mad2. This templated change in conformation is postulated as a mechanism for the amplification of the 'anaphase wait' signal. The two-step model proposes that the mitotic checkpoint complex (MCC) is the kinetochore-independent anaphase inhibitor, and the role of the unaligned kinetochore is to sensitize the anaphase-promoting complex/cyclosome (APC/C) to MCC-mediated inhibition.
Chan
Gordon K
GK
Department of Oncology, Faculty of Medicine & Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 1Z2. gordonch@cancerboard.ab.ca
Liu
Song-Tao
ST
Yen
Tim J
TJ
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D018797:Cell Cycle Proteins / Q000502:physiology; D020090:Chromosome Segregation / Q000502:physiology; D006801:Humans; D018386:Kinetochores / Q000378:metabolism / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000502:physiology; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D043743:Ubiquitin-Protein Ligase Complexes / Q000502:physiology
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome