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italianoActivity Report IFOM 2006
During the year 2006 scientists at IFOM published 99 research articles on international journals, totalling an average impact factor of 8.778. [
impact factor]
- "SUMO": the DNA defender
- ONCOGENES: crazy guys behind the wheel of the cells
- INCREASED ALCOHOLIC RISK if the gene EPS8 is missing
"SUMO": the DNA defender
Among the 2006 publications it is worth to mention a research paper published last November by the international journal Cell, carried out by Dana Branzei and Marco Foiani (research programme: Cell Cycle control and Genome Integrity).
"Ubc9- and Mms21-Mediated Sumoylation Counteracts Recombinogenic Events at Damaged Replication Forks" (Branzei et al., Cell, 2006, PMID: 17081974; impact factor 29.431)
Credit:
Felipe Colasanti Risco
IFOM scientists, working in collaboration with an international team (including the RIKEN Discovery Research Institute in Wako, Japan) and with scientists from the University of Milan, have characterized and described for the first time the role of a specific protein named SUMO (Small Ubiquitin-like Modifier), a molecule which is able to shield the cells from those chromosomal alterations that lead to cancer development. Helped as it is by a group of enzymes, SUMO prevents the accumulation of "aberrant structures" on DNA during chromosome replication. In doing so, it prohibits the proliferation of damaged cells that could give rise to severe diseases such as tumours and metastases. These findings clarify one of the two key mechanisms in charge of controlling the genome stability, and suggests potential critical applications on the therapeutic side, as it spots a new "therapeutic target" that could be used, relatively soon, in the efforts against cancer. Besides, as underlined by Dana Branzei, "sumolation is a precious aid, that protects specifically against the genetic damage we may incur into when the cells undergo stressful conditions, such as during anticancer therapies. Inactivate the sumolation process and you'll end up without protection. Unveiling the mechanism of action of sumolation could help us to optimize the conventional therapies, choosing specific ones according to the genetic profile of each patient."
ONCOGENES: crazy guys behind the wheel of the cells
A critical breakthrough in basic research but also, as in this case, important clinical repercussions stem from the research published last November 2006 by Nature, carried out by Raffaella Di Micco and Marzia Fumagalli under the supervision of Fabrizio d'Adda di Fagagna (group leader of the programme Telomeres and senescence):"Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication" (Di Micco et al., Nature, 2006, PMID: 17136094; impact factor 29.273)
Modification of a senescent cell showing DNA damage foci
The investigation, carried out in collaboration with the European Institute of Oncology, the National Cancer Institute, Aviano (PN), and the Institute Pasteur in Paris, unveiled the link between the direct activity exerted on the cell cycle by the oncogenes and the activation of specific signals of "response to the genetic damage" (DDR or DNA Damage Response), which actually represent a sort of "molecular brake" the cells use to avoid the dissemination of mistakes affecting their DNA. [ oncogenes] By markedly accelerating the cell cycle, the scientists proved that oncogenes are the major culprits of brakes occurring to DNA detriment, and that this is a critical event in tumour onset. "In our opinion, - commented D'Adda di Fagagna - this discovery steps forward the comprehension of the basic mechanisms leading to tumour development. It will be of potential help during the designing of effective diagnostic tests for early spotting of cancer.
IFOM press release: ONCOGENES: crazy guys behind the wheel of the cells (November 29th, 2006 -
.pdf 149 Kb, italian language)
INCREASED ALCOHOLIC RISK if the gene EPS8 is missing
Extremely relevant is also the investigation carried out by a team of scientists led by Nina Offenhäuser and Pier Paolo Di Fiore, in a collaborative effort with research groups at IEO, University of Milan, University of Pavia, Neurological Institute Carlo Besta (Milan), University of California and the Karolinska Institutet in Stockholm.
"Increased ethanol resistance and consumption in eps8 knockout mice correlates with altered actin dynamics" (Offenhauser et al., Cell 2006, PMID: 17018287; impact factor 29.431)
This research deserved the cover of the journal Cell, by proving that any lack of the gene Eps8 increases the risk of alcoholism. This scientific result correlates for the first time some genetic determinants of alcoholism to a physiologic cellular process involving the cytoskeleton, the proteinic scaffold that sustains the cells allowing their movements. Animal models devoid of the gene Eps8 exhibit a phenotype which is indistinguishable from the human condition of alcoholism. The work by Offenhäuser and colleagues moved from the analysis of a family of genes (to whom Eps8 belongs) that are suspected to be involved in the neoplastic transformation and in tumour progression. These results open up new therapeutic perspectives: some of them correlate to alcoholism (for example, it's been already a few years since some USA investigations highlighted a direct correlation between high ethanol consumption and mammary tumours), others are more generally linked to pathologies where the molecular mechanisms that play a pivotal role in inter- and intra-cellular communication - such as the one where Eps8 is involved - do not work properly. Cancer is a typical such pathology.
Another research focused on the Eps8 gene and on the protein it codes for. In this investigation the scientists analysed the molecular interactions involved in defining the very cellular structure.
"Regulation of cell shape by Cdc42 is mediated by the synergic actin-bundling activity of the Eps8-IRSp53 complex" (Disanza et al., Nature Cell Biology 2006, PMID: 17115031; impact factor 19.717).
IFOM press release: Alcoholism risk without the Eps8 Gene (October 6th, 2006 -
.86 Kb - italian language)
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