Methods to identify USP1 deubiquitinating enzyme complex inhibitors

An in vitro, biochemical method of identifying an inhibitor of ubiquitin specific protease 1(USP1) comprising:

• (i) contacting an isolated USP1 with a test compound in the presence of monoubiquitinated proliferating cell nuclear antigen (PCNA) or ubiquitin-7-amido-4-methylcoumarin,
• wherein said USP1 is selected from the group consisting of SEQ ID NO:
• 3 or the polypeptide set forth by amino acids 17-785 of SEQ ID NO:
• 3, and wherein said PCNA comprises SEQ ID NO:
• 2;
• and
• (ii) detecting the deubiquitination of said PCNA or ubiquitin-7-amido-4-methylcoumarin using an antibody or fluorescence,
• wherein a decrease in the deubiquitination of said PCNA or ubiquitin-7-amido-4-methylcoumarin in the presence of the test compound, relative to the absence of the test compound, identifies said test compound as an inhibitor of USP1.