UBIQUITIN SIGNALS IN REGULATION OF DNA REPAIR

抄録

The attachment of a ubiquitin (Ub) to a substrate serves as an important regulatory modification implicated in receptor endocytosis, virus budding, gene transcription, DNA repair and replication, etc. The discovery of Ub-binding domains (UBDs) has indicated how Ub can regulate such distinct cellular functions. We have recently cloned two novel Ub-binding domains named UBM (Ub binding motif) and UBZ (Ub binding Zn finger), which are evolutionarily conserved in Y-family translesion polymerases (pols). These domains are required for binding of pols to Ub, their accumulation in replication factories and interaction with monoubiquitinated PCNA. In addition, Ub-binding domains of Y-family polymerases play essential roles for in vivo translesion synthesis, which is the major pathway by which mammalian cells replicate across DNA lesions. Interestingly, novel Ub-binding domains are found in several other proteins implicated in regulation of DNA repair and replication.In addition to binding Ub, several UBDs promote monoubiquitination of host proteins. Biochemical, biophysical and mathematical evidence support the concept whereby monoubiquitination of the Ub binding proteins facilitates intramolecular interactions with the UBDs, thus preventing them from binding in trans to ubiquitinated targets. Monoubiquitination of Ub-binding proteins thus represents a regulatory mechanism that inhibits their capacity to bind to and control functions of ubiquitinated targets in vivo. [J Physiol Sci. 2006;56 Suppl:S66]