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

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, SY., Dufficy, E.R. et al. (2021) Arginine methylation and ubiquitylation crosstalk controls DNA end-resection and homologous recombination repair. Nature Communications 12, 6313. https://doi.org/10.1038/s41467-021-26413-6

PubMed ID

34728620 (pubmed)

Additional Links

https://doi.org/10.1038/s41467-021-26413-6

Type

Journal article

Language

en

Description

©2021 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link: https://doi.org/10.1038/s41467-021-26413-6

ISSN

2041-1723

EISSN

2041-1723

Rights

Licence for published version: Creative Commons Attribution 4.0 International

cb

Collections

Faculty of Science and Engineering