DNA Repair Helps Treat Genetic Disorders

Judith Campbell, a professor of chemistry and biology at Caltech, has discovered some interesting new insights into treatments for a bone marrow genetic disorder.

Through the investigation of two genes--FANCD2 and DNA2--which are both known to play roles in fixing broken or damaged strands of DNA within a cell of DNA repair, a defective version of the FANCD2 gene can result in the genetic disease Fanconi anemia (FA) that translates to failure of the bone marrow and an inability to replenish the body's blood cell supply. This can also prelude to certain developmental disorders and even cancers. Though there has not yet been a definite connection between the FA and DNA2 families, genetic studies implicate DNA2 in the FA DNA repair pathway.

Researchers examined the relationship between the genes by applying formaldehyde and three other DNA-damaging substances to three types of cells, according to a press release: "those lacking FANCD2, those lacking DNA2, and cells lacking both FANCD2 and DNA2."

Results showed that for cells where only one of the two genes had been deleted were quickly affected by the formaldehyde. The cells that did not have FANCD2 and DNA2, however, were able to repair from the DNA damage and go on.

"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 FA patients," said Kenneth Karanja, a former postdoctoral scholar in Campbell's laboratory and first author on the study. Currently, the only treatment for FA is a bone marrow transplant, but even after the transplant the disease remains lethal, via the release.

"DNA2 is a well-studied gene, and this recent discovery could potentially become the basis for ameliorating the symptoms of this incurable disorder," Campbell added, noting that the protein DNA2 encodes is a promising drug target.

"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 an FA patient's cancer predisposition-as well as a possible gene therapy for aiding a patient's blood cell development."

More information regarding the findings can be seen via the journal Cell Cycle.