Two of the unique events that occur in meiosis are high levels of genetic recombination and the reductional division. Our previous work demonstrated that the REC102, REC104, REC114, and RAD50 genes, required to initiate meiotic recombination in Saccharomyces cerevisiae, are needed for the proper timing of the first meiotic (MI) division. If these genes are absent, the MI division actually begins at an earlier time. This paper demonstrates that the meiotic recombination genes MER2/REC107, SPO11, and MRE2 and the synaptonemal complex genes HOP1 and RED1 are also required for the normal delay of the MI division. A rec103/ski8 mutant starts the MI division at the same time as in wild-type cells. Our data indicate no obvious correlation between the timing of premeiotic S phase and the timing of the first division in Rec ؊ mutants. Cells with rec102 or rec104 mutations form MI spindles before wild-type cells, suggesting that the initiation signal acts prior to spindle formation. Neither RAD9 nor RAD24 is needed to transduce the signal, which delays the first division. The timing of the MI division in RAD24 mutants indicates that the pachytene checkpoint is not active in Rec ؉ cells and suggests that the coordination between recombination and the MI division in wild-type cells may occur primarily due to the initiation signal. Finally, at least one of the targets of the recombination initiation signal is the NDT80 gene, a transcriptional regulator of middle meiotic gene expression required for the first division.Chromosomes passing through meiosis undergo a specific sequence of events that does not occur in mitotic cells. These events include an S phase that may well be unique to meiosis, high levels of genetic recombination, formation of the synaptonemal complex (SC), a reductional division, and an equational division that is not immediately preceded by an S phase (27,33,41). It has become clear that these meiotic events are coordinated, not only through a sophisticated temporal regulation of gene expression (5,23,36), but also by the existence of meiotic checkpoints that assess whether events have occurred properly (e.g., reference 42). A checkpoint in prophase I has been studied in detail and has been referred to variously as the pachytene checkpoint and the recombination checkpoint (18,29).At least two types of defects can be recognized by the pachytene checkpoint: defects caused by mutations in some late recombination genes such as dmc1 (i.e., "late" because they act after the formation of double strand breaks [DSBs]) and defects caused by mutations in some SC genes such as zip1. In such mutant strains, cells arrest in late prophase and do not undergo the first meiotic (MI) division. The ability to establish the checkpoint depends on the presence of part of the mitotic DNA damage checkpoint system; RAD24 and RAD17 are required for the arrest (29, 42). In contrast, RAD9 (which is required for the mitotic checkpoint) does not play a role in the pachytene checkpoint. Evidence suggests that the long singlestrand tails ...

Meiosis is the process by which diploid cells undergo DNA synthesis, homologous recombination and pairing, followed by the reductional division then the equational division. I present work in this PhD thesis which furthers the understanding of the coordination of the initiation of meiotic recombination and the reductional division. Ten genes are required to initiate recombination in Saccharomyces cerevisiae. The presence of a subset of recombination initiation proteins creates a Recombination Initiation Signal (RIS) that delays the start of MI in wild type cells. I present experiments demonstrating the first division kinetics of the two remaining recombination initiation genes that our lab had not yet studied. Rec107 is part of the RIS, while Ski8 is not. The RIS is conserved in a divergent Saccharomyces strain background. rec102 and rec104 SK1 strains both start the first division earlier that wild type SK1 strains. I present evidence that suggests that the RIS acts independently of the pathway that controls securin (PDS1) degradation. The work in this thesis expands our knowledge of the mechanism by which the RIS delays the reductional division. In this thesis I present experiments showing that the DNA damage, spindle and S phase checkpoints do not transduce the RIS. I establish the meiosis-specific candidate Mek1 as a candidate for relaying the RIS. Lastly, experiments described in these chapters show that the transcriptional activator of Middle Meiosis, NDT80, is the target of the RIS. NDT80 transcription and activity are both necessary and sufficient to affect an earlier reductional division, similar to the early MI seen in RIS mutants.