Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair

Pilar Sanchez-Bailon, Soo Choi, Elizabeth Dufficy, Karan Sharma, Gavin McNee, Emma Gunnell, Kelly Chiang, Debashish Sahay, Sarah Maslen, Grant Stewart, Mark Skehel, Ingrid Dreveny, Clare Davies

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Abstract

Cross-talk between distinct protein post-translational modifications is critical for an effective DNA damage response. Arginine methylation plays an important role in maintaining genome stability, however how this modification integrates with other enzymatic activities is largely unknown. Here, we identify the deubiquitylating enzyme USP11 as a previously uncharacterised PRMT1 substrate, and demonstrate that the methylation of USP11 promotes DNA end-resection and the repair of DNA double strand breaks by homologous recombination (HR), an event that is independent from another USP11-HR activity, the deubiquitylation of PALB2. Interestingly, we also show that PRMT1 is a ubiquitylated protein that it is targeted for deubiquitylation by USP11, which regulates the ability of PRMT1 to bind to and methylate MRE11. Taken together, our findings reveal a specific role for USP11 during the early stages of DSB repair, which is mediated through its ability to regulate the activity of the PRMT1-MRE11 pathway.
Original languageEnglish
Article number6313
Number of pages18
JournalNature Communications
Volume12
Issue number1
Early online date2 Nov 2021
DOIs
Publication statusPublished - Dec 2021

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