Salvage Pathways Recovering Mono-ubiquitin Adducts and Recycling Polyubiquitin

Salvage Pathways Recovering Mono-ubiquitin Adducts and Recycling Polyubiquitin 

Regulating mono-ubiquitination of proteins by DUBs is important in histone modification where ubiquitination is thought to modulate chromatin structure and transcriptional activity. Normally, about 10% of the histone core octomers contain ubiquitinated histones and the ubiquitin is removed at mitosis by DUB activity. UBP8 has been demonstrated to regulate the ubiquitination of histone H2B, which is important in transcriptional activation of many genes [88]. 

One fascinating observation is that PCNA (proliferating cell nuclear antigen) can be modified by multiple forms of ubiquitin, demonstrating that DUBs with different specificities can act at the same location on a specific substrate. PCNA can be modified by mono-ubiquitin, 63-linked polyubiquitin, or SUMO at K164 [89]. Modification of PCNA by mono- or polyubiquitin determines whether it is utilized in translesion synthesis or error-free DNA repair, respectively. SUMO modification prevents PCNA function in DNA repair and instead promotes DNA replication. It is probable that multiple DUBs, as yet unidentified, are required to regulate PCNA modification. 

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