The successful production of gametes during meiosis requires chromosomes to replicate and segregate in a precisely determined manner through two consecutive rounds of chromosome alignment and separation. The molecular events regulating chromosome cohesion are not fully understood. We have identified a gene, gei-17, which when depleted in C. elegans results in several defects including a delay in chromosome separation during meiosis. I propose to characterize the nature of the meiotic defect and the biochemical function of the GEl-17. Using mutant strains of C. elegans with defined meiotic defects we will determine what stage of meiosis is impaired in gei-17 RNAi animals. GEl-17 shares significant homology with known SUMO ligases, enzymes responsible for conjugating SUMO to proteins. I will first determine if GEl-17 can sumoylate proteins in a cell culture assay using C. elegans homologs of known substrates for GEl-17-related SUMO ligases. I will identify novel substrates for GEl-17 by screening proteins that when depleted result in chromosome nondisjunction. These experiments will define the stage of meiosis GEl-17 is involved in and define the physiological role of GEl-17 by identifying its enzymatic function and substrates.
|Leach, Craig A; Michael, W Matthew (2005) Ubiquitin/SUMO modification of PCNA promotes replication fork progression in Xenopus laevis egg extracts. J Cell Biol 171:947-54|