Differential roles for the spindle assembly checkpoint in error surveillance and mitotic timing.

Mad2 becomes dispensable for viability in SAC-deficient Cdc20 ∆FL cells, even though SAC components show synthetic-lethal interactions with chromosome segregation genes.

• Why it matters: The work tests whether SAC proteins primarily surveil mitotic errors or instead function as a timer for anaphase onset, addressing a key mechanistic gap.
• What they did: Using a CRISPR/Cas9 screen in Cdc20 ∆FL cells, the authors mapped genetic interactions and then targeted pathways controlling mitotic timing, including Mad2 inhibition, Cdk1-mediated Cdc20 phosphorylation, and total Cdc20 levels.
• The result: Combining perturbations of these timing controls causes premature mitotic exit and catastrophic chromosome mis-segregation, while Mad2 specifically is not required for viability in Cdc20 ∆FL cells.