1. Regulation of monoubiquitinated PCNA by DUB autocleavage.
- Author
-
Huang TT, Nijman SM, Mirchandani KD, Galardy PJ, Cohn MA, Haas W, Gygi SP, Ploegh HL, Bernards R, and D'Andrea AD
- Subjects
- Amino Acid Sequence, Arabidopsis Proteins, DNA Replication, Endopeptidases chemistry, Endopeptidases genetics, Fanconi Anemia Complementation Group G Protein genetics, Fanconi Anemia Complementation Group G Protein physiology, Humans, Molecular Sequence Data, Protein Processing, Post-Translational, Sequence Homology, Amino Acid, Ubiquitin-Specific Proteases, Ultraviolet Rays, DNA Damage radiation effects, Endopeptidases metabolism, Gene Expression Regulation, Proliferating Cell Nuclear Antigen metabolism, Ubiquitin metabolism
- Abstract
Monoubiquitination is a reversible post-translational protein modification that has an important regulatory function in many biological processes, including DNA repair. Deubiquitinating enzymes (DUBs) are proteases that are negative regulators of monoubiquitination, but little is known about their regulation and contribution to the control of conjugated-substrate levels. Here, we show that the DUB ubiquitin specific protease 1 (USP1) deubiquitinates the DNA replication processivity factor, PCNA, as a safeguard against error-prone translesion synthesis (TLS) of DNA. Ultraviolet (UV) irradiation inactivates USP1 through an autocleavage event, thus enabling monoubiquitinated PCNA to accumulate and to activate TLS. Significantly, the site of USP1 cleavage is immediately after a conserved internal ubiquitin-like diglycine (Gly-Gly) motif. This mechanism is reminiscent of the processing of precursors of ubiquitin and ubiquitin-like modifiers by DUBs. Our results define a regulatory mechanism for protein ubiquitination that involves the signal-induced degradation of an inhibitory DUB.
- Published
- 2006
- Full Text
- View/download PDF