PhD defence L. (Lieke) Koornneef

Below is a brief summary about the dissertation:

Meiosis is a specialized cell division to generate haploid gametes, and this requires two cell divisions called meiosis I and II. Special to meiosis I is the formation of programmed breaks in the DNA, whereby the DNA repair is crucial. This generates a physical connection between homologous chromosomes which in turn is needed for the first cell division. At the same time, that DNA repair also causes exchange between the maternal and paternal genome, resulting in beneficial genetic diversity in the offspring. This only succeeds when DNA repair proceeds via homologous recombination by using the homologous chromosome as a template for repair. In mice, the mechanism behind this interhomolog bias is poorly understood because of the lack of suitable research methods. At least, the proteins RAD51 and its meiosis-specific paralogue DMC1 (also called recombinases) play an important role in the DNA exchange during the meiotic prophase. To facilitate DNA repair, the homologous chromosomes also need to align with their partner (synapsis), a process of which details are also unclear. To understand the role of the recombinases in relation to synapsis, this thesis has used a detailed microscopic approach to investigate the localization of proteins RAD51 and DMC1 as well as the role of BRCA2 in loading of both recombinases during meiotic prophase I in mice.