Two Distinct Surveillance Mechanisms Monitor Meiotic Chromosome Metabolism in Budding Yeast

Meiotic recombination is initiated by Spo11-generated DNA double-strand breaks (DSBs) [1]. A fraction of total DSBs is processed into crossovers (CRs) between homologous chromosomes, which promote their accurate segregation at meiosis I (MI) [2]. The coordination of recombination-associated events and MI progression is governed by the "pachytene checkpoint" [3], which in budding yeast requires Rad17, a component of a PCNA clamp-like complex, and Pch2, a putative AAA-ATPase [3-7]. We show that two genetically separable pathways monitor the presence of distinct meiotic recombination-associated lesions: First, delayed MI progression in the presence of DNA repair intermediates is suppressed when RAD17 or SAE2, encoding a DSB-end processing factor [8, 9], is deleted. Second, delayed MI progression in the presence of aberrant synaptonemal complex (SC) is suppressed when PCH2 is deleted. Importantly, ZIP1, encoding the central element of the SC [10], is required for PCH2-dependent checkpoint activation. Analysis of the rad17Δ pch2Δ double mutant revealed a redundant function regulating interhomolog CR formation. These findings suggest a link between the surveillance of distinct recombination-associated lesions, control of CR formation kinetics, and regulation of MI timing. A PCH2-ZIP1-dependent checkpoint in meiosis is likely conserved among synaptic organisms from yeast to human [6, 11].