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

Sanchez-Bailon, Maria Pilar; Choi, Soo Youn; Dufficy, Elizabeth R.; Sharma, Karan; McNee, Gavin S.; Gunnell, Emma; Chiang, Kelly; Sahay, Debashish; Maslen, Sarah; Stewart, Grant S.; Skehel, J. Mark; Dreveny, Ingrid; Davies, Clare C.

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, but 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 (DSB) by homologous recombination (HR), an event that is independent from another USP11-HR activity, the deubiquitylation of PALB2. 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.

Citation

Sanchez-Bailon, M. P., Choi, S. Y., Dufficy, E. R., Sharma, K., McNee, G. S., Gunnell, E., Chiang, K., Sahay, D., Maslen, S., Stewart, G. S., Skehel, J. M., Dreveny, I., & Davies, C. C. (2021). Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair. Nature Communications, 12(1), Article 6313. https://doi.org/10.1038/s41467-021-26413-6

• Journal Article Type: Article
• Acceptance Date: Oct 4, 2021
• Online Publication Date: Nov 2, 2021
• Publication Date: Dec 1, 2021
• Deposit Date: Sep 8, 2022
• Publicly Available Date: Sep 8, 2022
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 1
• Article Number: 6313
• DOI: https://doi.org/10.1038/s41467-021-26413-6
• Keywords: General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/6681867
• Publisher URL: https://www.nature.com/articles/s41467-021-26413-6