Chromosome segregation during meiosis

During meiosis haploid gametes are produced from a diploid cell in contrast to mitosis where ploidy of dividing cells remains unchanged. There are three major features of meiotic chromosomes which ensure the meiotic chromosome segregation. The first is recombination where homologous chromosomes cross over to form chiasmata. The second meiosis specific feature is mono-orientation of sister kinetochores. The third meiosis specific feature is protection of centromeric cohesion during meiosis I. While the recombination is relatively well understood and our recent identification of the Sgo1 (shugoshin) shed the light on the protection of centromeric cohesion, we know close to nothing about the mechanism how sister kinetochores mono-orient during the first meiotic division. Our project aims to identify proteins required for mono-orientation of sister kinetochores during the first meiotic division. This will help us to elucidate the mechanism how chromosomes segregate during meiosis. We designed a genetic screen which we want to use to identify mutants defective in the mono-orientation process in the model organism fission yeast Schizosaccharomyces pombe. In addition, in a candidate approach we would like to investigate a possible role of the Hhp1 and Hhp2 kinases in this process. Our preliminary data suggest that Hhp1 and Hhp2 together with their S. cerevisiae homolog Hrr25 are proteins conserved throughout the evolution required for the mono-orientation of sister kinetochores during the first meiotic division.

Sexual reproduction depends on the generation of gametes (e.g. sperm cells or eggs) from precursor cells. This process called meiosis is achieved by two successive rounds of nuclear division during which chromosome number is halved. The main aim of our work is to contribute to our understanding of molecular mechanisms governing segregation of chromosomes during meiosis. In this project, we focused on kinetochores (protein complex assembled on centromeric chromatin and site of microtubule attachment) which determine the pattern of chromosome segregation. We used the model organism fission yeast S. pombe and combination of genetic and biochemical techniques to identify novel factors and to study proteins known to be involved in chromosome segregation during meiosis. We found that meiotic recombination (the process by which genetic information between maternal and paternal chromosomes is exchanged) plays important role in orientation of sister kinetochores during the first meiotic division. In the second part of our project, we focused on two proteins called Hhp1 and Hhp2. We found that these proteins localize to centromeric regions of chromosome and they play important role in orientation of sister kinetochores during the first meiotic division. We identified proteins interacting with Hhp1 and Hhp2 and showed that one of these proteins (Rec8) is modified by Hhp1 or Hhp2. Our further experiments revealed that this Hhp1/Hhp2-dependent modification (phosphorylation) of Rec8 is crucial for proper segregation of chromosomes during the first meiotic division. These observations not only reveal important molecular details about the regulation of meiosis, but may also provide important implications for human health and fertility. It is well established that defects in chromosome segregation during meiosis are the major cause of miscarriages, birth defects, infertility and genetic disorders such as Down syndrome. Finally, this FWF grant established our independent research group, which now consists of several young scientists who are fully devoted to pushing forward the frontiers of knowledge through cutting-edge research.