Understanding the mechanisms of histone 2A ubiquitination

textabstractUbiquitination is a post-translational modification widely used by the cell to regulate function, fate and localization of proteins. While in some cases the cellular and molecular functions are known, in other instances the molecular details of the ubiquitin signaling remain obscure. Understanding the structural and biochemical details of these processes is key to the possibility of use them in targeted therapy. This thesis presents new molecular insights into the mechanisms of histone H2A ubiquitination. Modification of H2A is crucial in the epigenetic transcriptional silencing by Polycomb proteins as well as in the DNA damage response pathway. Here we describe differences and similarities of the biochemical machineries involved in catalyzing these ubiquitin modifications on H2A