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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM071231-02
Application #
6875234
Study Section
Special Emphasis Panel (ZRG1-F08 (20))
Program Officer
Portnoy, Matthew
Project Start
2004-03-08
Project End
2007-03-07
Budget Start
2005-03-08
Budget End
2006-03-07
Support Year
2
Fiscal Year
2005
Total Cost
$48,296
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
082359691
City
Cambridge
State
MA
Country
United States
Zip Code
02138