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The deubiquitinating enzyme USP1 contains highly conserved motifs forming its catalytic center. Recently, the COSMIC mutation database identified a mutation in USP1 at Asp‐199 in endometrial cancer. Here, we investigated the role of Asp‐199 for USP1 function. The mutation of aspartic acid to alanine (D199A) resulted in failure of USP1 to undergo autocleavage and form a complex with ubiquitin, indicating...
The Fanconi anemia (FA) pathway regulates DNA interstrand crosslink (ICL) repair. A critical step in this pathway is mono‐ubiquitination of FANCD2 (FANCD2‐Ub). Deubiquitinase USP1 removes ubiquitin from FANCD2 resulting in inactivation of the FA pathway. USP1 is autocleaved and subsequently degraded for its down‐regulation. Here, we investigated the functional consequences of Usp1‐autocleavage defect...
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