View Program - 63rd Annual Drosophila Research Conference

Crossing-over between homologous chromosomes is a critical part of meiosis that prevents aneuploidy by promoting proper segregation of chromosomes. By facilitating accurate disjunction of homologs, crossing-over forestalls miscarriages and chromosomal disorders such as Down syndrome, the risk of which increases with maternal age. Meiotic crossovers (COs) are formed from programmed double-strand breaks (DSBs) that undergo homologous recombination. Although the DSBs that initiate crossing-over are distributed throughout the chromosome, intricate patterning governs where COs are placed. Three types of patterning events have been observed, one of which is the centromere effect (CE) that ensures CO exclusion in the regions surrounding the centromere. The CE is crucial to the meiotic cell, as centromere-proximal COs increase risk of nondisjunction. Despite its importance, the mechanisms behind this patterning event are poorly understood. To address this gap in knowledge, I will investigate the mechanisms underlying the CE using Drosophila as a model system. Pericentric heterochromatin in Drosophila is not homogenous and is instead divided into two classes: the heterochromatin closer to the centromere (alpha heterochromatin) consists of highly repetitive satellite arrays, while that adjacent to euchromatin (beta heterochromatin) is less repetitive with some amount of unique sequence. Recent work from our lab has shown that the CE in Drosophila manifests as a complete exclusion of COs in alpha heterochromatin, and we hypothesize that this could be due to an absence of DSBs in this region. To test this, I will study differences in the number and positioning of DSBs in flies with heterochromatin defects, as compared to wild type. Recent work from our lab has also suggested that the CE in beta heterochromatin and proximal euchromatin is distance dependent. I will investigate whether this distance effect is based on distance from the centromere, or alpha heterochromatin, by deleting a large satellite array from the pericentric regions of the X chromosome. This will not only remove a large segment of alpha heterochromatin, but also move beta heterochromatin and proximal euchromatin closer to the centromere. Measuring CO rates in these regions will determine how the CE in proximal euchromatin and beta heterochromatin is influenced by proximity to alpha heterochromatin and the centromere. Another avenue that I plan on investigating is the sensitivity of the CE to the number of centromeres. I will study this by measuring crossover rates in flies that have a reduced total number of centromeres through the use of compound chromosomes. Through these and other methods, my overarching goal is to gain more understanding of the mechanisms at work behind crossover patterning, particularly the exclusion of crossovers near the centromere.

Meiotic Crossover Patterning: The Centromere Effect