Fig. 2. A hypothetical model for the interplay between DNA polymerases involved in replication and translesion DNA synthesis. During DNA synthesis, the DNA replication machinery [schematically drawn as the pol / holoenzyme (pol /, RF-C, and PCNA)], eventually meets lesions on the DNA (represented with black symbols). Pol and are unable to traverse DNA lesions and their arrest causes the block of the replication fork. The current model predicts the existence of subnuclear compartments or foci (the `garages' in the drawing), where replicative or translesion (TLS) polymerases and their cognate auxiliary proteins are stored. When a replication fork stalls, checkpoints are activated leading to the recruitment of specific factors at the lesion through a yet unidentified machinery (drawn as an `auxiliary crane'). Consequently, replicative polymerases are lifted off and replaced by specialised TLS pols by a `polymerase crane'. After damage bypass, the normal replication machinery is reconstituted through an inverse mechanism. PCNA constitutes the common element to all these pathways, providing essential interactions with both replicative and TLS polymerases, as well as acting in the checkpoint process.