The Coordination of Recombination Initiation and the First Division in Meiosis

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Meiosis is the highly conserved, special cell division process in which gametes are made in eukaryotes. Meiotic chromosome events, premeiotic DNA synthesis, recombination and synapsis, the first reductional division, the second equational division, and packaging (into sperm, eggs, spores, etc.) all must be coordinated and occur in the right order and time. Dr. Malone's long range goal is to understand chromosome behavior in meiosis, and the goal of this project is specifically to understand the coordination between two steps unique to, and essential for, meiosis: recombination and the first meiotic chromosome division. This research explores the possibility that functions involved at the start of recombination modulate the subsequent separation of chromosomes. In the yeast S. cerevisiae (and other organisms), two methods of coordinating these two steps are well known: the recombination checkpoint monitoring later stages of genetic recombination, and the spindle checkpoint, monitoring spindle-kinetochore attachment and chromosome tension (to which recombination contributes). This investigator has found evidence for another mode of coordination involving the presence of a subset of the gene products required to initiate recombination, evidence that wild type cells recognize the presence of these gene products and respond by delaying the expression of a regulator (NDT80) required for the first division. Dr. Malone hypothesizes that the eight initiation functions required form a signal that modulates NDT80 expression and hence division. He tests this hypothesis by asking the following three questions: 1) Do initiation proteins interact with patterns consistent with their effects on the timing of first chromosome separation; 2) Is the proposed pathway truly separable from the spindle checkpoint, known to be involved in recognizing unrecombined chromosomes; and 3) How do cells sense the presence of the initiation proteins and modulate NDT80 expression?This research will shed light on how chromosomes (the genetic information) behave when they go through the process (meiosis) that leads, in "higher cells", to the generation of sex cells such as sperm and eggs. This process is absolutely required for the alteration of generations of all higher cells, and the majority of nonbacterial cells. The investigator has data indicating that two special events that only happen during meiosis are coregulated. The work presented here tests this hypothesis. Since meiosis is the basis of genetics for all higher cells, understanding of the mechanism of meiosis is central to truly understanding genetics. Thus the research here not only addresses a basic biological mechanism, but it generates information applying to a major scientific approach--genetics. In addition to the contribution to basic knowledge of living systems, the research will allow the training of new young scientists, both as graduate students and as undergraduates; this is critical for the nation to maintain its position in the world of science. In addition, the funding will allow the laboratory to participate in the scientific training of minority students during both the school year and the summer.