SUMMARY Faithful genome transmission during cell division requires precise, coordinated action of DNA metabolic enzymes, including proteins responsible for DNA damage detection and repair. Dynamic phosphorylation plays an important role in controlling repair enzymes during the DNA damage response (DDR). Cdc14 phosphatases oppose cyclin-dependent kinase (Cdk) phosphorylation and have been implicated in the DDR in several model systems. Using new insight into Cdc14 specificity we identified the budding yeast Holliday junction resolvase Yen1 as the first DNA repair target of Cdc14. Cdc14 activation at anaphase triggers nuclear accumulation and enzymatic activation of Yen1, likely to resolve persistent recombinational repair intermediates. Consistent with this, expression of a phosphomimetic Yen1 mutant increased sister chromatid non-disjunction. In contrast, lack of Cdk phosphorylation resulted in constitutive activity and elevated crossover-associated repair. The precise timing of Yen1 activation, governed by core cell cycle regulators, helps coordinate DNA repair with chromosome segregation and safeguards against genome destabilization.

Background: Mediator is a conserved eukaryotic transcriptional coregulatory complex. Results: Disruption of two putative Mediator subunits leads to hyperaccumulation of phenylpropanoids, metabolites important to both the fitness of plants and their utility to humans. Conclusion: Mediator is essential in plants for the maintenance of phenylpropanoid homeostasis. Significance: Functional dissection of Mediator is critical to understand eukaryotic transcription and to rationally engineer plant metabolic pathways.

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Inactivation of cyclin-dependent kinase (Cdk) and reversal of Cdk phosphorylation are universally required for mitotic exit. In budding yeast (), Cdc14 is essential for both and thought to be the major Cdk-counteracting phosphatase. However, Cdc14 is not required for mitotic exit in many eukaryotes, despite highly conserved biochemical properties. The question of how similar enzymes could have such disparate influences on mitotic exit prompted us to re-examine the contribution of budding yeast Cdc14. By using an auxin-inducible degron, we show that severe Cdc14 depletion has no effect on the kinetics of mitotic exit and bulk Cdk substrate dephosphorylation, but causes a cell separation defect and is ultimately lethal. Phosphoproteomic analysis revealed that Cdc14 is highly selective for distinct Cdk sites and does not catalyze widespread Cdk substrate dephosphorylation. We conclude that additional phosphatases likely contribute substantially to Cdk substrate dephosphorylation and coordination of mitotic exit in budding yeast, similar to in other eukaryotes, and the critical mitotic exit functions of Cdc14 require trace amounts of enzyme. We propose that Cdc14 plays very specific, and often different, roles in counteracting Cdk phosphorylation in all species.