Fanconi anemia is a rare genetic disease characterized by high cancer risk. Researchers of the University of Würzburg now have revealed a new Fanconi anemia gene that is involved in complex DNA repair processes and may also play a relevant role in cancer prevention.
Fanconi anemia is a rare genetic disease characterized by bone marrow failure heralded by low platelet counts and unusually large red blood cells. Mutations in over 20 genes have been identified as causative for Fanconi anemia, which encode proteins commonly involved in DNA repair mechanisms.
The failure to repair DNA is considered the source of increased cancer risk in individuals with Fanconi anemia. Ongoing efforts to identify additional genes and pathways linked to this disease may concurrently reveal potential susceptibility genes for hereditary cancers.
This week in the Journal of Clinical Investigation (JCI), a team led by Detlev Schindler at the Julius-Maximilians-Universität (JMU) Würzburg in Bavaria, Germany, reports classical Fanconi anemia symptoms in a 12-year-old individual without mutations in any of the known Fanconi anemia genes.
Sequencing of this individual’s genome detected mutations in both alleles of the gene RFWD3, which encodes an enzyme that helps target other proteins on single-stranded DNA for degradation. This process is impaired in patient’s cells which rendered them more sensitive to chromosome breakage and DNA damage, compared to cells from healthy individuals.
Other cells either lacking RFWD3 or genetically engineered with the patient’s missense mutation showed similar DNA repair defects, which were rescued by expression of wild-type RFWD3. Moreover, RFWD3-deficient mice exhibited a phenotype that resembles other mouse models of Fanconi anemia. Together, these findings support the identification of RFWD3 as a Fanconi anemia gene.
„Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia“, Kerstin Knies, Shojiro Inano, María J. Ramírez, Masamichi Ishiai, Jordi Surrallés, Minoru Takata, and Detlev Schindler. Journal of Clinical Investigation, 10. July 2017, DOI: 10.1172/JCI92069
Schindler and collaborators further describe the mechanisms by which RFWD3 mediates DNA repair in two accompanying studies recently published in Molecular Cell. Future explorations of this enzyme may reveal its importance as a therapeutic target in certain subtypes of Fanconi anemia or cancer.
Prof. Dr. Detlev Schindler, Institute of Human Genetics, University of Würzburg, Germany, T +49 931 31-88075, firstname.lastname@example.org
http://www.jci.org/articles/view/92069 Publication in the Journal of Clinical Investigation
https://doi.org/10.1016/j.molcel.2017.04.022 Publication 1 in „Molecular Cell“
http://dx.doi.org/10.1016/j.molcel.2017.04.021 Publication 2 in „Molecular Cell“
Robert Emmerich | Julius-Maximilians-Universität Würzburg
Multifunctional bacterial microswimmer able to deliver cargo and destroy itself
26.04.2018 | Max-Planck-Institut für Intelligente Systeme
ADP-ribosylation on the right track
26.04.2018 | Max-Planck-Institut für Biologie des Alterns
Magnetic resonance imaging, or MRI, is a widely used medical tool for taking pictures of the insides of our body. One way to make MRI scans easier to read is...
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
26.04.2018 | Physics and Astronomy
26.04.2018 | Life Sciences
26.04.2018 | Medical Engineering