Local control of meiotic chromosome fragmentation and repair
Dr. Vader's lab studies how cells maintain genomic stability during meiosis, the specialized cell division that is essential for sexual reproduction. Meiosis-specific events dictate the formation of haploid germ cells (gametes; sperm and egg in most species) from a diploid precursor cell. In most organisms, including humans, the reduction of chromosome number to a haploid complement requires the controlled fragmentation and reshuffling of parental chromosomes. This is achieved by the generation of hundreds of DNA double strand breaks and their repair by homologous recombination. Although required for meiotic chromosome segregation and a driving force of genetic diversity and evolution, chromosome reshuffling also jeopardizes the stability of the genome.
DNA breaks are non-randomly introduced into the genome; there are so-called DNA hot and cold spots. Certain regions of the genome are particularly at-risk during DNA break repair. For example, incorrect recombination within repetitive sequences and within regions close to centromeres often results in genome destabilization and aneuploidy in the gametes. In humans, meiotic genome destabilization and aneuploidy are associated with genetic disorders and birth defects, such as autism spectrum disorders and Down syndrome. It is therefore important to define the basic workings of the meiotic program and, specifically, the mechanisms that shape the meiotic DNA break landscape. The processes of meiotic DNA formation and recombination are strongly conserved, and we are using the budding yeast Saccharomyces cerevisiae as a system to study the general principles behind the generation of proper gametes.
For more information : http://gerbenvader.wixsite.com/meiosis
Max Planck Institute of Molecular Physiology, Dortmund, Germany