The Huntington's disease (Huntington's Disease, HD) is a hereditary nuerodegenerativa pathology, in which a particular sequence of three nucleotides (CAG), is "expanded", that is inserted in multiple copies at the beginning of the Huntingtin protein gene. When the number of these triplets exceeds a threshold value, the resulting protein in neurons assumes its pathological form, causing the degeneration of neurons. The mechanism by which the number of CAG triplets is expanded is not perfectly known. The study conducted by the DNA Enzymology group of Dr. Giovanni Maga and Dr. Emmanuel Crespan, IGM-CNR, together with Prof.. Ulrich Hubscher, University of Zurich, has identified a possible expansion mechanism related to the repair of DNA breaks by the DNA polymerase beta.
When the DNA break occurs at the level of the CAG repeats, DNA polymerase beta was seen to repair the breakage adding multiple copies of the repeat, which is thus expanded. This polymerase is the only one to be significantly expressed in adult neurons and is overexpressed in HD patients. It is the first time that a role of DNA polymerase beta in the repair of DNA breaks and in the genesis of Huntington's disease is proposed. If confirmed, new directions for understanding the pathogenesis of this disease could be provided.
Focus