Cells and More Cells : The American Society for Cell Biology Washington, DC December 8–12, 2001

Fanconi anemia (FA) and Ataxia Telangiectasia (AT) are two cancer-susceptibility disorders caused by a breakdown of DNA repair systems. Until now the two syndromes shared some basic similarities but no components. Now, however, Alan D'Andrea and colleagues at the Dana-Farber Cancer Center in Boston, MA, find that one protein is directly involved in both diseases.

When wild-type cells are exposed to DNA cross-linking agents, a DNA repair pathway is initiated. The FA complex, consisting of protein subunits encoded by five FA-linked genes, becomes active and monoubiquitinates the FANCD2 protein. Once monoubiquitinated, FANCD2 is recruited to a BRCA1 complex and DNA repair begins.

Mutations in any one of eight FA-linked genes can block this process, leading to an increased sensitivity to DNA cross-linking and an overall increased rate of chromosome breakage. In earlier work, D'Andrea's team found that...