The study will appear online during the week of Sept. 14, 2003, and is scheduled for publication in the October 2003 edition of the journal Nature Genetics.
Scientists found that inactivation of the newly discovered protein, PHF9, disables the function of the FA pathway, a network of proteins that appears to be critical for many cellular processes, including repair of damaged DNA, blood development and fertility.
"What's intriguing about the proteins in the Fanconi pathway is that they don't contain familiar sequences, so until the discovery of PHF9, there have been very few clues about how they actually function," said Maureen Hoatlin, Ph.D., assistant professor of molecular medicine in the Oregon Health & Science University School of Medicine, who worked to isolate and characterize the function of PHF9 with colleagues at the National Institute on Aging; Free University Medical Center, Amsterdam; and the Baylor College of Medicine.
The isolation of PHF9 demonstrates a new way of recognizing FA genes by using direct analysis of the components contained in the Fanconi protein complex, Hoatlin said. Previously, several Fanconi genes were discovered by finding their positions on chromosomes, or by going to a library of genes to select one that would correct the defects.
PHF9 is a member of a multicomponent Fanconi protein complex. It is believed to trigger the function of another FA protein, FANCD2, discovered and cloned in February 2001 by Markus Grompe, M.D., professor of molecular and medical genetics, and pediatrics in the OHSU School of Medicine. When the function of PHF9 is disrupted, FANCD2 is not modified, and the pathway short-circuits, leading to the disease hallmarks of FA.