Molecular anchor links the 2 inheritable diseases Fanconi anemia and Bloom's syndrome

Dec 24, 2009

A new study establishes a molecular link that bridges two rare inherited disorders and explains why these diseases result in genetic instability. The research, published by Cell Press in the December 24th issue of the journal Molecular Cell, may lead to a better understanding of the complex mechanisms that enable cells to repair damaged DNA.

Fanconi Anemia (FA) and Bloom's Syndrome (BS) are unique rare genetic disorders that have some key characteristics in common. Both FA and BS are associated with disrupted repair mechanisms and an elevated predisposition for cancer. The genetic mutations that cause FA and BS have been identified and, importantly, the associated with both FA and BS affect large complexes composed of several proteins (the FA and BS core complexes) that mediate key DNA repair processes.

"There is strong clinical and biochemical evidence suggesting that FA and BS proteins may act in a common DNA repair pathway," explains study author Dr. Stephen C. West from the London Research Institute. "However, the specific interactions are poorly understood." Dr. West and co-author, Dr. Andrew J. Deans, examined the FA gene FANCM because it has been shown to directly bind to DNA and has been shown to have specificity for substrates that are similar to those linked with the BS core complex.

The researchers identified two regions in the FANCM protein that enabled it to physically link the FA core complex and the BS complex. FA and BS complexes bound independently to FANCM, but not with each other in the absence of FANCM. The researchers went on to show that a disruption of the interaction between the two core complexes and FANCM led to similar chromosomal repair defects representative of both BA and FA cells.

"We have shown for the first time that FANCM acts as a molecular scaffold that functions in a variety of repair reactions and serves as a bridge between FA and BS. The biological and clinical implications of this link are likely to be important in relation to the phenotypes associated with these genetic disorders," explains Dr. West. "Further understanding how these interactions and reactions are regulated should provide a more complete understanding of the molecular basis of FA and BS."

Explore further: Study identifies genetic change in autism-related gene

Provided by Cell Press search and more info website

not rated yet
add to favorites email to friend print save as pdf

Related Stories

'Fluorescent' cells give early warning for eye disease

Feb 22, 2008

Scientists at the University of Michigan have shown that their new metabolic imaging instrument can accurately detect eye disease at a very early stage. Such a device would be vision-saving because many severe eye diseases ...

New understanding of DNA repair

Feb 16, 2006

A mechanism by which genes are repaired has been described in detail for the first time. This new understanding may, in the long term, provide the scientific foundation upon which therapies to treat genetic diseases or cancers ...

Recommended for you

Mutation disables innate immune system

20 hours ago

A Ludwig Maximilian University of Munich team has shown that defects in the JAGN1 gene inhibit the function of a specific type of white blood cells, and account for a rare congenital immune deficiency that ...

Study identifies genetic change in autism-related gene

Aug 28, 2014

A new study from Bradley Hospital has identified a genetic change in a recently identified autism-associated gene, which may provide further insight into the causes of autism. The study, now published online in the Journal of ...

NIH issues finalized policy on genomic data sharing

Aug 27, 2014

The National Institutes of Health has issued a final NIH Genomic Data Sharing (GDS) policy to promote data sharing as a way to speed the translation of data into knowledge, products and procedures that improve health while ...

The genes behind the guardians of the airways

Aug 27, 2014

Dysfunctions in cilia, tiny hair-like structures that protrude from the surface of cells, are responsible for a number of human diseases. However the genes involved in making cilia have remained largely elusive. ...

User comments : 0