The long-term goal of this project is to determine mechanisms cells use for normal DNA function and maintenance in meiosis. All of the mechanisms cells use for this purpose are not known. The primary objective of this project is to determine and understand functions of the BLM5 gene of Saccharomyces cerevisiae in maintaining normal eukaryotic DNA function in meiosis. The blm mutants of S. cerevisiae were isolated on the basis of their hypersensitivity to killing by ionizing radiation, H2O2, and the bleomycin and phleomycin chemical families. Meiosis is defective in heterozygous BLM5/blm5-1 and homozygous blm5-1/ blm5-1 mutant diploid cells. Objectives of this project include determining 1) the role of the BLM5 gene in maintaining normal chromosomal structure and function in meiosis, 2) how the BLM5 gene functions with other genes in meiosis, 3) genes, gene products and functions that complement the blm5 mutation in meiosis, and 4) the relationship between chromosomal lesions in meiosis and viability. The proposed research integrates interrelated studies at the cellular and molecular levels, using genetic characterizations, molecular biology and biochemistry. The genetic sophistication, molecular flexibility and availability of mutant strains of S. cerevisiae permit these studies and technical approaches. Studies of the blm mutants will contribute important basic knowledge on normal DNA function and maintenance during meiosis.
