Two distinct surveillance mechanisms monitor meiotic chromosome metabolism in budding yeast.
Meiotic recombination is initiated by Spo11-generated DNA double-strand breaks (DSBs) . A fraction of total DSBs is processed into crossovers (CRs) between homologous chromosomes, which promote their accurate segregation at meiosis I (MI) . The coordination of recombination-associated events and MI progression is governed by the "pachytene checkpoint", which in budding yeast requires Rad17, a component of a PCNA clamp-like complex, and Pch2, a putative AAA-ATPase . 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 , 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 , is required for PCH2-dependent checkpoint activation. Analysis of the rad17Deltapch2Delta 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 .
Wu
Hsin-Yen
HY
Section of Molecular and Cellular Biology, Genetics Graduate Group, University of California, Davis, Davis, California 95616, USA.
Burgess
Sean M
SM
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D015825:Chromosomes, Fungal / Q000378:metabolism*; D003434:Crossing Over, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases; D008540:Meiosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013573:Synaptonemal Complex / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C501395:RAD17 protein, S cerevisiae; C107849:SAE2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C090118:Zip1 protein, S cerevisiae; C069930:rad9 protein; D004720:Endonucleases