Why does (sometimes) meiosis fail? Lessons from yeast to prevent gamete aneuploidy

Resumen del trabajo presentado al International Symposium: Yeasts as versatile testbeds for the Life Sciences, celebrado en Madrid (España) del 17 al 18 de octubre de 2016.Meiosis is the specialized cell division that produces haploid gametes from diploid parental cells (gametogenesis). During meiosis, a single phase of DNA replication is followed by two consecutive rounds of chromosome segregation, resulting in the reduction of the ploidy by half. After fertilization, the normal chromosome complement is restored; therefore, the accuracy in the distribution of chromosomes to the gametes is critical for a healthy offspring and species survival. Meiotic errors result in aneuploidy and, in humans, they are the main cause of pathologies associated to reproduction, leading to fertility disorders, spontaneous abortions or genetic birth defects, such as, for example, Down's syndrome. During meioisis, the processes of pairing, synapsis and recombination are crucial to establish physical connections between homologous chromosomes that orchestrate their segregation during the first meiotic division. Given the importance of these events, meiotic cells have developed surveillance mechanisms (checkpoints) that monitor proper distribution of genetic material to the progeny. This meiotic checkpoint network blocks meiotic cell cycle progression in response to defects in recombination and/or chromosome synapsis, thus preventing aberrant chromosome segregation and the formation of aneuploid gametes. Importantly, the incidence of aneuploidy in humans is higher than in other organisms; in fact, about 10% of natural pregnancies harbor monosomic or trisomic embryos; this proportion significantly increases with the maternal age. Although several factors are involved, a weaker checkpoint response to face meiotic errors is one of the causes contributing to this high frequency of human aneuploidy. Therefore, investigating the molecular mechanisms underlying the control of meiotic chromosome dynamics by checkpoints is fundamental to understand the causes of pregnancy losses, infertility and genetic birth diseases. The budding yeast Saccharomyces cerevisiae possesses robust meiotic quality control systems. Given the evolutionary conservation of checkpoint pathways and the proteins involved, as well as the ample array of research tools available, this is an excellent model system to make progress in the understanding of the molecular basis of fertility problems. We will present our advances in the knowledge of the checkpoint mechanisms employed by yeast meiotic cells to respond to recombination and chromosome synapsis defects.Peer Reviewe