ubiquitin carboxyl-terminal hydrolase 1; deubiquitinating enzyme 1; hUBP; ubiquitin thiolesterase 1; ubiquitin-specific-processing protease 1 (USP1)
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Function
- negative regulator of DNA damage repair
- specifically deubiquitinates monoubiquitinated FANCD2
- also involved in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA
- has almost no deubiquitinating activity by itself & requires interaction with WDR48 to have a high activity
- thiol-dependent hydrolysis of ester, thioester, amide, peptide & isopeptide bonds formed by the C-terminal Gly of ubiquitin
- autocatalytic cleavage of USP1 following UV irradiation inactivates it leading to an increase in ubiquitinated PCNA, recruitment of POLH & translesion synthesis
- ubiquitinated; leading to its subsequent proteasomal degradation (putative)
- phosphorylated upon DNA damage, probably by ATM or ATR
- interacts with FANCD2 & PCNA
- interacts with WDR48
- KM=0.7 uM for ubiquitin vinyl sulfone (in presence of WDR48)
- KM=1.4 uM for ubiquitin vinyl sulfone (in absence of WDR48)
Structure
belongs to the peptidase C19 family
Compartment
Expression
- cell cycle-regulated
- highest level during S phase
- induced down-regulated following DNA damage
Pathology
- HEK293T cells expressing reduced levels of USP1 show a higher level of ubiquitinated PCNA & an increase in point mutations upon UV irradiation