Summary of Work: This project is designed to determine the relationships among DNA repair, chromosome structure, and mutagenesis in Drosophila melanogaster. Mutations that increase the mutant frequency (mutators) have been identified in the mu2 gene and characterized. Irradiated oocyte chromosomes are not repaired properly. Instead, broken chromosomes are "capped" with a new telomere in the zygote after fertilization. Irradiated sperm chromosomes are repaired normally under the same conditions. Thus, it appears that DNA, per se, is active in mu2 mutant females, but the oocyte chromosomes are not amenable to repair. Given that mu2 mutations also increase mitotic recombination and the mu2 gene is expressed in mitotically active somatic cells, it is expected that the MU2 protein also associates with somatic chromosomes. The mu2 gene sequence does not have a strong resemblance to any other genes in the database. The conceptual protein has three nuclear localization signals; a helix-loop-helix domain adjacent to a short basic region, suggesting protein and/or DNA binding activity; and a BRCT (BRCA1 carboxy terminal) domain, a protein-binding region found in many DNA repair/recombination/cell cycle control proteins. The project will terminate at the end of the year.