Studying the function of the BRCA2 gene

Thousands, perhaps hundreds of thousands, women have had a genetic test for the BRCA1 and BRCA2 mutations association with higher risk for breast cancer. So far, it's been difficult to determine exactly what the genes do in humans, other than interfere with the function of two suppressors apparently needed to properly manage DNA replication and repair.

A recent article in PLOS Genetics, an open-access, peer-reviewed online journal, describes some experiments that have been conducted with the common fruit fly, Drosophila melanogaster, which also has a BRCA2 gene. The article is titled "Drosophila brca2 is Required for Mitotic and Meiotic DNA Repair and Efficient Activation of the Meiotic Recombination Checkpoint" and the abstract reads as follows:

Heterozygous mutations in the tumor suppressor BRCA2 confer a high risk of breast and other cancers in humans. BRCA2 maintains genome stability in part through the regulation Rad51-dependent homologous recombination. Much about its precise function in the DNA damage responses is, however, not yet known. We have made null mutations in the Drosophila homolog of BRCA2 and measured the levels of homologous recombination, non-homologous end-joining, and single-strand annealing in the premeiotic germline of Drosophila males. We show that repair by homologous recombination is dramatically decreased in Drosophila brca2 mutants. Instead, large flanking deletions are formed and repair by the non-conservative single-strand annealing pathway predominates. We further show that during meiosis, Drosophila Brca2 has a dual role in the repair of meiotic double-stranded breaks and the efficient activation of the meiotic recombination checkpoint. The eggshell patterning defects that result from activation of the meiotic recombination checkpoint in other meiotic DNA repair mutants can be strongly suppressed by mutations in brca2. In addition, Brca2 coimmunoprecipitates with the checkpoint protein Rad9, suggesting a direct role for Brca2 in the transduction of the meiotic recombination checkpoint signal.

The full article is available in provisional form in the PLOS Genetics list of articles for 8 January 2008. Unless you are a geneticist fully involved in research of BRCA genes, or perhaps a Drosophila geneticist, you are unlikely to fully understand the article, or perhaps even the abstract. Don't despair. Scanning the article, you might find the connections between flies and mammals (humans) interesting, as well as the differences between the two groups.

I believe what is important is that a model now exists for studying the normal and mutated BRCA2 gene and the results of studies have been published in an open-access journal, available for anyone to read and use.

Marie Godfrey, PhD

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