Insights into the functions of BRCA1 and BRCA2.

Since BRCA1 and BRCA2 were cloned five years ago, unraveling their normal functions has posed fascinating problems for cancer biologists. Both genes are novel, and little of their normal function was revealed by their sequence. Both genes contribute to homologous recombination and DNA repair, to embryonic proliferation, to transcriptional regulation and, for BRCA1, to ubiquitination. But questions regarding BRCA1 and BRCA2 biology remain, and their resolution is critical for clinical development. Why do ubiquitously expressed genes that participate in universal pathways lead, when mutant, specifically to breast and ovarian cancer? Why are the same genes required for embryonic proliferation and for tumor suppression?

Paternal effects in Drosophila: implications for mechanisms of early development.

The study of paternal effects on development provides a means to identify sperm-supplied products required for fertilization and the initiation of embryogenesis. This review describes paternal effects on animal development and discusses their implications for the role of the sperm in egg activation, centrosome activity, and biparental inheritance in different animal species. Paternal effects observed in Caenorhabditis elegans and in mammals are briefly reviewed. Emphasis is placed on paternal effects in Drosophila melanogaster. Genetic and cytologic evidence for paternal imprinting on chromosome behavior and gene expression in Drosophila are summarized. These effects are compared to chromosome imprinting that leads to paternal chromosome loss in sciarid and coccid insects and mammalian gametic imprinting that results in differential expression of paternal and maternal loci. The phenotypes caused by several early-acting maternal effect mutations identify specific maternal factors that affect the behavior of paternal components during fertilization and the early embryonic mitotic divisions. In addition, maternal effect defects suggest that two types of regulatory mechanisms coordinate parental components and synchronize their progression through mitosis. Some activities are coordinated by independent responses of parental components to shared regulatory factors, while others require communication between paternal and maternal components. Analyses of the paternal effects mutations sneaky, K81, paternal loss, and Horka have identified paternal products that play a role in mediating the initial response of the sperm to the egg cytoplasm, participation of the male pronucleus in the first mitosis, and stable inheritance of the paternal chromosomes in the early embryo.

The faint band/interband region 28C2 to 28C4-5(-) of the Drosophila melanogaster salivary gland polytene chromosomes is rich in transcripts.

Urate oxidase mRNA and five other transcripts map along 38 kb of DNA in the region 28C on the Drosophila melanogaster second chromosome. Three biotinylated restriction fragments from this 38 kb of DNA, one from each end and one from the middle, were individually hybridized in situ to slightly stretched salivary gland polytene chromosomes. The data from these in situ hybridizations in combination with the transcription map of the 38 kb of DNA indicate that: (i) there are six discrete RNA species encoded along the 38 kb of DNA and (ii) these six transcripts map to the faint band/interband region which includes the proximal edge of 28C1, the three faint bands, 28C2, 28C3 and 28C4-5(-), and the adjacent interband chromatin. Our data are consistent with the few published studies directly demonstrating that faint band/interband regions of the Drosophila melanogaster salivary gland polytene chromosomes code for a high density of transcripts.