Ubiquitinating enzymes catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzymes action. There are five DUB subfamilies including the USP, UCH, OTU, MJD, and JAMM enzymes. USP1 belongs to the USP subfamily and is regulated in a cell cycle dependent manner by both transcriptional and ubiquitin-proteosomal mechanisms. USP1 is a nuclear protein and localizes to chromatin where it is specifically associated with FANCD2. USP1 deubiquitinates monoubiquitinated FANCD2, which plays an important role in DNA damage repair and Chk1 protein stability. Another important target of USP1 is PCNA. USP1 deubiquitinates monoubiquitinated PCNA, thereby negatively regulating PCNA-mediated translesion synthesis during DNA repair. USP1 interaction with UAF1, a WD40 repeat-containing protein, leads to formation of an activated USP1/UAF1 complex, which is required for the deubiquitinase activity of USP1.
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