DNA damage repair and chromosome synapsis in meiosis

We are interested in understanding the crucial steps leading to faithful chromosome segregation during meiosis. Meiosis is a specialized cell division resulting in the production of gametes (e.g. eggs and sperm). This division concludes in the reduction of the number of chromosomes by half.

Upon fertilization, the number of chromosomes is restored so that it is identical to the one found in the parental cells. The accurate reconstitution of chromosome numbers is crucial for the development of a healthy embryo. Alterations in chromosome numbers are the leading known causes for serious birth defects including Down syndrome as well as miscarriages and stillbirths. Therefore, the accurate separation of homologous chromosomes during meiosis is key event for successful sexual reproduction and is of tremendous importance for human health.

During meiotic prophase I, the two homologous chromosomes (one each of paternal and of maternal origin) separate. Formation of a physical link between homologous chromosomes prior to their segregation is required for this accurate separation. This link is mediated via crossovers, the exchange of genetic material between the homologous chromosomes. To ensure the production of at least one obligatory crossover, the synaptonemal complex (SC) is formed between each pair of homologous chromosomes. In the absence of a functional SC, recombination is impaired and chromosomes missegregate in cells that proceed to the meiotic division.

The formation of the SC regulates the repair of meiotically induced double strand breaks (DSBs) to form crossovers. Therefore DNA damage repair is crucial for successful meiosis and in its absence DNA damage and chromosome missegregation occur.