Abstract：
:Proper segregation of the replicated genome requires that kinetochores form and maintain bioriented, amphitelic attachments to microtubules from opposite spindle poles and eliminate erroneous, syntelic attachments to microtubules from the same spindle pole. Phosphorylation of kinetochore proteins destabilizes low-tension kinetochore-microtubule attachments, yet tension stabilizes bioriented attachments. This conundrum for forming high-tension amphitelic attachments is recognized as the "initiation problem of biorientation (IPBO)." A delay before kinetochore-microtubule detachment solves the IPBO, but it lacks a mechanistic framework. We developed a stochastic mathematical model for kinetochore-microtubule error correction in yeast that reveals: (1) under low chromatin tension, requiring a large number of phosphorylation events at multiple sites to achieve detachment provides the necessary delay; and (2) kinetochore-induced microtubule depolymerization generates tension in amphitelic, but not syntelic, attachments. With these requirements, the model provides a mechanistic framework for the delay before detachment to solve the IPBO and demonstrates the high degree of amphitely observed experimentally for wild-type spindles under optimal conditions.
journal_name
Cell Systjournal_title
Cell systemsauthors
Tubman ES,Biggins S,Odde DJdoi
10.1016/j.cels.2017.05.003subject
Has Abstractpub_date
2017-06-28 00:00:00pages
645-650.e5issue
6eissn
2405-4712issn
2405-4720pii
S2405-4712(17)30182-5journal_volume
4pub_type
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