Mechanistic Insights into the Multiple Activities of the Rad5 Family of Enzymes

The budding yeast protein Rad5 is highly conserved among eukaryotes. Rad5 and its orthologs including helicase like transcription factor (HLTF) and SNF2 histone linker PHD RING helicase (SHPRH) in humans constitute a unique family of enzymes that play critical roles in the cellular response to DNA replication stresses. The function of the Rad5 family of enzymes is fulfilled by their multiple activities, including ubiquitin ligase, replication fork regression activities and others. Herein, we review recent studies that provided mechanistic insights into their multiple activities and their coordination.