The long range objective of this research proposal is to determine the molecular mechanisms that govern gene transmission during meiosis. Although this process plays a central role in the generation of genetic variation and the production of gametes with normal chromosome numbers, relatively little is known at the molecular level about the specific genes required for these events. The simple eucaryote, S. cerevisiae, is being used in these studies. The experimental program is specifically aimed at providing a molecular description of the structure, function and regulation of three genetically well-defined genes, SP011, SP012 and SP013, known to have important roles in meiotic chromosome behavior, as well as a fourth gene, SP016, which is closely linked to SP012 and is required for optimal levels of spore formation. The SP011 gene is necessary for meiotic recombination while SP012 and SP013 are each required for chromosome distribution at meiosis I. All four genes are transcriptionally induced during meiosis. The experimental approaches include: 1) in vitro mutagenesis of the regulatory regions to define cis-acting sequences responsible for meiosis-specific regulation, 2) mutant isolations to identify trans-acting factors that interact with these regions, 3) fusions to other yeast promoter-regulatory regions to determine how both time and level of expression affect meiotic and mitotic function, 4) purification of the proteins and the production of antibodies to study the properties and functions of the gene products and 5) searches for homologous genes in other eucaryotes to determine if these homologous genes have functions and regulation similar to the yeast genes.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD019252-04
Application #
3316477
Study Section
Genetics Study Section (GEN)
Project Start
1984-08-01
Project End
1992-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
4
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Houtteman, S W; Elder, R T (1993) A DNA polymerase mutation that suppresses the segregation bias of an ARS plasmid in Saccharomyces cerevisiae. Mol Cell Biol 13:1489-96
Honigberg, S M; Conicella, C; Espositio, R E (1992) Commitment to meiosis in Saccharomyces cerevisiae: involvement of the SPO14 gene. Genetics 130:703-16
Esposito, R E; Dresser, M; Breitenbach, M (1991) Identifying sporulation genes, visualizing synaptonemal complexes, and large-scale spore and spore wall purification. Methods Enzymol 194:110-31
Malavasic, M J; Elder, R T (1990) Complementary transcripts from two genes necessary for normal meiosis in the yeast Saccharomyces cerevisiae. Mol Cell Biol 10:2809-19
Gottlieb, S; Wagstaff, J; Esposito, R E (1989) Evidence for two pathways of meiotic intrachromosomal recombination in yeast. Proc Natl Acad Sci U S A 86:7072-6
Strich, R; Slater, M R; Esposito, R E (1989) Identification of negative regulatory genes that govern the expression of early meiotic genes in yeast. Proc Natl Acad Sci U S A 86:10018-22
Gottlieb, S; Esposito, R E (1989) A new role for a yeast transcriptional silencer gene, SIR2, in regulation of recombination in ribosomal DNA. Cell 56:771-6
Atcheson, C L; DiDomenico, B; Frackman, S et al. (1987) Isolation, DNA sequence, and regulation of a meiosis-specific eukaryotic recombination gene. Proc Natl Acad Sci U S A 84:8035-9
Wang, H T; Frackman, S; Kowalisyn, J et al. (1987) Developmental regulation of SPO13, a gene required for separation of homologous chromosomes at meiosis I. Mol Cell Biol 7:1425-35