IGBMC : Institut de la Génétique et de la Biologie Moléculaire et Cellulaire

After identifying amphiphysin 2 as a potential therapeutic target in some congenital myopathies, researchers in Jocelyn Laporte's team at the IGBMC (CNRS/Inserm/Université de Strasbourg) were able to specifically modulate the level of this molecule and to reduce all signs of a severe form of myopathy. These results, published on March 20, 2019, in the journal Science translational medicine, offer new therapeutic perspectives for these myopathies.

Among the various damages that DNA can suffer, double-stranded breaks are the most dangerous and lethal. In this study, researchers from Evi Soutoglou's team, including Tibor Pankotai, at the IGBMC (CNRS/Inserm/Université de Strasbourg) in collaboration with the University of Leiden in the Netherlands, described the mechanisms that block the expression of genetic information when DNA is damaged. They highlighted the key role of an enzyme, ubiquitin ligase WWP2, in this process. These results are published on the 2 May in the journal Genes & Development.

The assembly of proteins into large macromolecular complexes is essential to the viability of cells. However, since genes encoding proteins that constitute such multiprotein complexes are dispersed in the eukaryotic genome, it is difficult to understand how these subunits can assemble. In this study, Laszlo Tora's team at the IGBMC (CNRS/Inserm/Université de Strasbourg) determined a pathway for assembling mammalian transcription complexes (TFIID, SAGA and TREX-2), each composed of a large number of subunits. According to their observations, complex assembly would be carried out during the synthesis of the proteins that constitute these complexes. These results are published in Nature Communications on April 15, 2019. 

Patients with a combined form of xeroderma pigmentosum and Cockayne syndrome have a wide range of clinical characteristics, including photosensitivity of the skin, predisposition to cancer and developmental disorders. At the origin of this rare genetic disease, a mutation of a subunit of the gene encoding TFIIH that plays a key role both in gene transcription and in gene repair. By studying patients' cells, researchers from Frédéric Coin's team at the IGBMC (CNRS/Inserm/Unistra) showed that the interaction of the TFIIH complex with the GCN5 enzyme leads to an increase in the enzymatic activity of GCN5, resulting in an uncontrolled remodelling of the chromatin and an overexpression of a large number of genes that may cause certain symptoms in patients.These results are published on March 20, 2019 in the journal Nature Communication.