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The role of USP 1 autocleavage in DNA interstrand crosslink repair
Author(s) -
Kim Mira,
Kim Jung Min
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12060
Subject(s) - chemistry , dna , dna repair , microbiology and biotechnology , biophysics , biochemistry , biology
The Fanconi anemia ( FA ) pathway regulates DNA interstrand crosslink ( ICL ) repair. A critical step in this pathway is mono‐ubiquitination of FANCD 2 ( FANCD 2‐Ub). Deubiquitinase USP 1 removes ubiquitin from FANCD 2 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. Usp1‐autocleavage mutant (Usp1 GG / AA ) corrected the level of Fancd2‐Ub similar to Usp1 WT in Usp1 −/− MEF s. However, Usp1 GG / AA only partially rescued MMC sensitivity with defective Fancd2 foci formation and homologous recombination defect. Contrary to this, Usp1 GG / AA was capable of recovering UV resistance of Usp1 −/− MEF s to a similar extent with Usp1 WT . Taken together, our findings suggest that Usp1 regulation by autocleavage is critical for Usp1 to exert its function in ICL repair.