The role of USP1 autocleavage in DNA interstrand crosslink repair

FEBS Letters
Mira Kim, Jungmin Kim

Abstract

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. Usp1-autocleavage mutant (Usp1(GG/AA) ) corrected the level of Fancd2-Ub similar to Usp1(WT) in Usp1(-/-) MEFs. 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(-/-) MEFs 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.

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