Figure 11.

A model for Pch2 checkpoint function. (A) In unperturbed wild-type meiosis, nucleolar Pch2 excludes Hop1 from the rDNA preventing recombination at this chromosome XII array. In turn, chromosomal Pch2 dictates Hop1 discontinuous axis distribution sustaining proper synapsis and recombination. In the pch2 single mutant, Hop1 localizes to the nucleolar region and unwanted rDNA recombination occurs. Hop1 is also more abundant on chromosome axes disturbing normal recombination events that slightly increase Hop1-T318 phosphorylation. Nevertheless, most recombination defects of the pch2 mutant are only evident when DSBs are limiting (28,56). (B) In the synapsis-deficient zip1 mutant, Pch2 is absent from the chromosomes and concentrated in the rDNA. This configuration supports continuous distribution of Hop1 along unsynapsed axes and high levels of Hop1-T318 phosphorylation relaying the checkpoint signal to Mek1 activation. When PCH2 is deleted (or the ATPase inactivated), Hop1 loading and phosphorylation is impaired leading to inoperative checkpoint. (C) Despite the weakened Hop1/Mek1 activation, HOP1 overexpression in zip1 pch2 provides enough protein to restore high levels of global Hop1 phosphorylation and reinstate checkpoint function (see text for additional details).