National Institute on Aging (NIA) researchers have discovered a new gene, FANCM, which sheds light on an important pathway involved in the repair of damaged DNA.

Specifically, mutation in this gene is responsible for one of the forms of Fanconi anemia (FA), a rare genetic disorder that primarily affects children. Like many rare, inherited diseases, understanding this gene's role in the development of FA provides insights into other medical problems -- in this case, age-related conditions including ovarian and pancreatic cancers, as well as leukaemia, the researchers said. Discovery of this gene and its protein provides a potential target for the development of drugs that can prevent or alleviate FA and a variety of cancers.

"FA is a disease that appears to be the result of a breakdown in vital DNA repair mechanisms," Weidong Wang, a senior investigator in the NIA's Laboratory of Genetics, who led the study said adding, "Some scientists theorize that DNA damage, which gradually accumulates as we age, leads to malfunctioning genes and deteriorating tissues and organs as well as increased risk of cancer. We believe that this new gene, FANCM, may be a potent cog in the DNA repair machinery." Wang said, "It is possible that we could learn how to promote the function of DNA repair complexes and hereby prevent the age-related accumulation of DNA damage."

FANCM, like most genes, contains information for making a specific protein. The FANCM protein, part of the molecular machine called the FA core complex, is the only protein within this machine that affects DNA by enzyme activity (enzymes are proteins that encourage biochemical reactions, usually speeding them up). FANCM apparently provides an engine that moves the FA DNA repair machine along the length of DNA. It also is a key component of the complex that is switched "on" or "off" by phosphorylation, or the addition of a phosphate group to a protein, in response to DNA damage. In the future, researchers hope to use the newly-discovered activities of FANCM as targets to select drugs that enhance the FA DNA damage response for intervention in patients.

Fanconi anaemia, named for Swiss pediatrician Guido Fanconi, affects about 1 in every 300,000 children. If both parents have the same mutation in the same FA gene, each of their children has a one-in-four chance of inheriting the defective gene from both parents and developing FA or certain types of cancer.