title: The dynamics of signal amplification by macromolecular assemblies for the control of chromosome segregation.
abstract: The control of chromosome segregation relies on the spindle assembly checkpoint (SAC), a complex regulatory system that ensures the high fidelity of chromosome segregation in higher organisms by delaying the onset of anaphase until each chromosome is properly bi-oriented on the mitotic spindle. Central to this process is the establishment of multiple yet specific protein-protein interactions in a narrow time-space window. Here we discuss the highly dynamic nature of multi-protein complexes that control chromosome segregation in which an intricate network of weak but cooperative interactions modulate signal amplification to ensure a proper SAC response. We also discuss the current structural understanding of the communication between the SAC and the kinetochore; how transient interactions can regulate the assembly and disassembly of the SAC as well as the challenges and opportunities for the definition and the manipulation of the flow of information in SAC signaling.
authors.affiliation: Center for Biomedical Informatics, Harvard Medical School, Harvard University Boston, MA, USA.
authors.forename: Semin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Biological and Medical Sciences, Faculty of Health and Life Sciences, Oxford Brookes University Oxford, UK.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Bolanos-Garcia
keywords: cancer; cell cycle regulation; chromosome segregation; genome instability; kinetochore-microtubules network; protein-protein interactions; signal amplification; spindle assembly checkpoint (SAC)