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Two Distinct Surveillance Mechanisms Monitor Meiotic Chromosome Metabolism in Budding Yeast

2006; Elsevier BV; Volume: 16; Issue: 24 Linguagem: Inglês

10.1016/j.cub.2006.10.069

1879-0445

Hsin-Yen Wu, Sean M. Burgess,

Mitochondrial Function and Pathology

Meiotic recombination is initiated by Spo11-generated DNA double-strand breaks (DSBs) [1Keeney S. Mechanism and control of meiotic recombination initiation.Curr. Top. Dev. Biol. 2001; 52: 1-53Crossref PubMed Google Scholar]. A fraction of total DSBs is processed into crossovers (CRs) between homologous chromosomes, which promote their accurate segregation at meiosis I (MI) [2Page S.L. Hawley R.S. Chromosome Choreography: The meiotic ballet.Science. 2003; 301: 785-789Crossref PubMed Scopus (326) Google Scholar]. The coordination of recombination-associated events and MI progression is governed by the “pachytene checkpoint” [3Roeder G.S. Bailis J.M. The pachytene checkpoint.Trends Genet. 2000; 16: 395-403Abstract Full Text Full Text PDF PubMed Scopus (378) Google Scholar], which in budding yeast requires Rad17, a component of a PCNA clamp-like complex, and Pch2, a putative AAA-ATPase [3Roeder G.S. Bailis J.M. The pachytene checkpoint.Trends Genet. 2000; 16: 395-403Abstract Full Text Full Text PDF PubMed Scopus (378) Google Scholar, 4Hochwagen A. Amon A. Checking your breaks: Surveillance mechanisms of meiotic recombination.Curr. Biol. 2006; 16: R217-R228Abstract Full Text Full Text PDF PubMed Scopus (116) Google Scholar, 5Hochwagen A. Tham W.H. Brar G.A. Amon A. The FK506 binding protein Fpr3 counteracts protein phosphatase 1 to maintain meiotic recombination checkpoint activity.Cell. 2005; 122: 861-873Abstract Full Text Full Text PDF PubMed Scopus (107) Google Scholar, 6San-Segundo P.A. Roeder G.S. Pch2 links chromatin silencing to meiotic checkpoint control.Cell. 1999; 97: 313-324Abstract Full Text Full Text PDF PubMed Scopus (213) Google Scholar, 7Lydall D. Nikolsky Y. Bishop D. Weinert T. A meiotic recombination checkpoint controlled by mitotic checkpoint genes.Nature. 1996; 383: 840-843Crossref PubMed Scopus (50) Google Scholar]. 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 [8Prinz S. Amon A. Klein F. Isolation of COM1, a new gene required to complete meiotic double-strand break-induced recombination in Saccharomyces cerevisiae.Genetics. 1997; 146: 781-795Crossref PubMed Google Scholar, 9McKee A.H. Kleckner N. A general method for identifying recessive diploid-specific mutations in Saccharomyces cerevisiae, its application to the isolation of mutants blocked at intermediate stages of meiotic prophase and characterization of a new gene SAE2.Genetics. 1997; 146: 797-816Crossref PubMed Google Scholar], 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 [10Sym M. Engebrecht J. Roeder G.S. ZIP1 is a synaptonemal complex protein required for meiotic chromosome synapsis.Cell. 1993; 72: 365-378Abstract Full Text PDF PubMed Scopus (488) Google Scholar], 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 [6San-Segundo P.A. Roeder G.S. Pch2 links chromatin silencing to meiotic checkpoint control.Cell. 1999; 97: 313-324Abstract Full Text Full Text PDF PubMed Scopus (213) Google Scholar, 11Bhalla N. Dernburg A.F. A conserved checkpoint monitors meiotic chromosome synapsis in Caenorhabditis elegans.Science. 2005; 310: 1683-1686Crossref PubMed Scopus (164) Google Scholar].