Covalent attachment of ubiquitin residue is not only the proteasomal degradation signal, but also a widespread posttranslational modification of cellular proteins in eukaryotes. One of the most important targets of the regulatory ubiquitination are histones. Localization of ubiquitin residue in different regions of the nucleosome attracts a strictly determined set of cellular factors with varied functionality. Depending on the type of histone and the particular lysine residue undergoing modification, histone ubiquitination can lead both to transcription activation and to gene repression, as well as contribute to DNA repair via different mechanisms. An extremely interesting feature of the family of RING E3 ubiquitin ligases catalyzing histone ubiquitination is the striking structural diversity of the domains providing high specificity of modification very similar initial targets. It is obvious that further elucidation of peculiarities of the ubiquitination system involved in histone modification, as well as understanding of physiological role of this process in the maintenance of homeostasis of both single cells and the entire organism, will substantially expand the possibilities of treating a number of socially significant diseases.
Keywords: DNA damage response; E3 ubiquitin ligase; RING E3 ligase family; histone; post-translational modification; protein–protein interactions; ubiquitination.