TY - JOUR TI - The copy-number and varied strengths of MELT motifs in Spc105 balance the strength and responsiveness of the spindle assembly checkpoint AU - Roy, Babhrubahan AU - Han, Simon JY AU - Fontan, Adrienne Nicole AU - Joglekar, Ajit P A2 - Pines, Jon A2 - Akhmanova, Anna A2 - Pines, Jon A2 - Nilsson, Jakob VL - 9 PY - 2020 DA - 2020/06/01 SP - e55096 C1 - eLife 2020;9:e55096 DO - 10.7554/eLife.55096 UR - https://doi.org/10.7554/eLife.55096 AB - During mitosis, the Spindle Assembly Checkpoint (SAC) maintains genome stability while also ensuring timely anaphase onset. To maintain genome stability, the SAC must be strong to delay anaphase even if just one chromosome is unattached, but for timely anaphase onset, it must promptly respond to silencing mechanisms. How the SAC meets these potentially antagonistic requirements is unclear. Here we show that the balance between SAC strength and responsiveness is determined by the number of ‘MELT’ motifs in the kinetochore protein Spc105/KNL1 and their Bub3-Bub1 binding affinities. Many strong MELT motifs per Spc105/KNL1 minimize chromosome missegregation, but too many delay anaphase onset. We demonstrate this by constructing a Spc105 variant that trades SAC responsiveness for much more accurate chromosome segregation. We propose that the necessity of balancing SAC strength and responsiveness drives the dual evolutionary trend of the amplification of MELT motif number, but degeneration of their functionally optimal amino acid sequence. KW - mitosis KW - spindle assembly checkpoint KW - cell cycle KW - chromosome segregation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -