Credit: Tom Ellenberger
Understanding the interaction between 2 genes may be the key to better treatment of Fanconi anemia, according to a paper published in Cell Cycle.
Researchers investigated the relationship between FANCD2 and DNA2, 2 genes known to play roles in DNA repair.
A defective version of FANCD2 can result in Fanconi anemia. And although DNA2 has not been associated with a Fanconi anemia family
yet, genetic studies have implicated DNA2 in the Fanconi anemia DNA repair pathway.
With the current study, the researchers found that deleting either FANCD2 or DNA2 alone makes cells susceptible to DNA damage. But the deletion of both genes enables DNA repair.
“A key implication of this finding is the potential to manipulate DNA2 to improve the survival of FANCD2-deficient cells, and hopefully, by extension, the survival of [Fanconi anemia] patients,” said study author Kenneth Karanja, PhD, a former postdoctoral scholar at the California Institute of Technology in Pasadena.
To uncover the relationship between the genes, Dr Karanja and his colleagues applied DNA-damaging substances—formaldehyde and cisplatin—to 3 types of cells: those lacking FANCD2, those lacking DNA2, and cells lacking both genes.
The groups of cells in which only 1 of the 2 genes had been deleted quickly succumbed to the substance-induced DNA damage. However, the cells lacking both FANCD2 and DNA2 were able to repair the DNA damage and survive.
So the researchers concluded that depletion of DNA2 in FANCD2-deficient cells reverses the cells’ sensitivity to DNA-damaging substances. And this finding may have implications for Fanconi anemia treatment.
“DNA2 is a well-studied gene, and this recent discovery could potentially become the basis for ameliorating the symptoms of this incurable disorder,” said study author Judith Campbell, PhD, of the California Institute of Technology.
“Since much is known about the mechanism of action of DNA2, it is an attractive target for future drug treatments—like small-molecule inhibitors that could reduce [a Fanconi anemia] patient’s cancer predisposition—as well as a possible gene therapy for aiding a patient’s blood cell development.”
