Newly Discovered Gene Sheds Light on Causes of Cancer, Rare Disease
August 22, 2005
Gene Discovery Sheds Light on Causes
of Rare Disease, Cancer
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 genes
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 leukemia, 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.
The finding is scheduled for advanced online publication
in Nature Genetics (http://www.nature.com/ng/) during
the week of August 21, 2005.* The report also will be
published in the journals September 2005 print edition.
The NIA is a component of the National Institutes of
Health (NIH) at the U.S. Department of Health and Human
FA is a disease that appears to be the result of a
breakdown in vital DNA repair mechanisms, said Weidong
Wang, Ph.D., a senior investigator in the NIAs Laboratory
of Genetics, who led the study. 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 thereby 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 anemia, 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. The disease
leads to bone marrow failure (aplastic anemia) and is
associated with birth defects such as missing or extra
thumbs and skeletal abnormalities of the hips, spine,
or ribs. Many who have FA eventually develop acute myeloid
leukemia and are prone to head and neck, gastrointestinal,
and other cancers. The first symptoms, such as nose
bleeds or easy bruising, usually begin before age 12.
In rare instances, however, symptoms do not become apparent
until adulthood. This is the third FA gene and protein
combination identified in the last 3 years by Wang and
In addition to the NIA, researchers were supported
by the FA Research Fund in Eugene, OR, the Daniel Ayling
Fanconi Anemia Trust, the Dutch Cancer Society, and
the Netherlands Organization for Health Research and
Please note: Dr. Wang will be available for interviews
The NIA is one of 27 institutes and centers at the
NIH. The Institute leads Federal efforts to support
and conduct basic, clinical, epidemiological, and social
research on aging and the special needs of older people.
Press releases, fact sheets, and other materials about
aging and aging research can be viewed at the NIAs
general information web site, www.nia.nih.gov.
The National Institutes of Health (NIH) — The
Nation’s Medical Research Agency — is comprised
of 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services.
It is the primary Federal agency for conducting and
supporting basic, clinical, and translational medical
research, and investigates the causes, treatments,
and cures for both common and rare diseases. For more
information about NIH and its programs, visit http://www.nih.gov.
*AR Meetei et al, A Human Orthologue of Archaeal DNA Repair
Protein Hef is Defective in Fanconi Anemia Complementation Group
M, Nature Genet., August 21, 2005, online.
This is a NIH news release. The original version appears here