27 January 2012 00:00 hrs.
Protecting the genome during gametogenesis

Dr. Gerben Vader, Whitehead Institute for Biomedical Research Nine Cambridge Center, Cambridge, USA


Dr. Joop Jansen, department of  Central Hematology Laboratory, RUNMC

27-01-2012 00:00:00Europe/AmsterdamProtecting the genome during gametogenesis

Remarks / more information:

Vader , GerbenSexual reproduction requires the production of gametes (sperm and egg in humans) containing a haploid chromosome content. Gametes are the product of meiosis, a specialized cell division program during which several meiosis-specific events dictate the formation of haploid reproductive cells from a diploid progenitor cell. In most organisms, 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 (DSBs) 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. Certain regions of the genome are particularly at-risk during DSB repair. For example, incorrect recombination within repetitive sequences and within regions close to centromeres often results in genome destabilization and aneuploidy in the gametes. I will discuss my recent finding of a novel protective mechanism that shields the budding yeast ribosomal rDNA array from meiotic DSB formation. I found that the edges of the rDNA array are exceptionally susceptible to meiotic DSBs, necessitating a border-specific protection system consisting of the conserved meiotic ATPase Pch2 and the origin recognition complex subunit Orc1. Upon disruption of these factors, DSB formation and recombination specifically increased in the outermost rDNA repeats, leading to rDNA instability. In addition, I will also present ongoing experiments aimed at understanding the mechanisms that prevent unwanted recombination events close to centromeres. In humans, meiotic genome destabilization and aneuploidy are associated with genetic disorders and birth defects, such as autism spectrum disorders and Down syndrome. Therefore, it is important to understand how at-risk regions within the genome are protected against unwanted meiotic DSB formation and recombination.

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