CARM1/PRMT4 facilitates XPF–ERCC1 heterodimer assembly and maintains nucleotide excision repair activity
The structure-specific endonuclease, XPF-ERCC1, plays a central role in DNA damage repair. This nuclease is known to be important for nucleotide excision repair, interstrand crosslink repair, and DNA double-strand repair. We found that the arginine methyltransferase, CARM1/PRMT4, is essential for XPF stabilization and maintenance of intracellular protein levels. Loss of CARM1 results in a decrease in XPF protein levels and a concomitant decrease in ERCC1 protein. A similar destabilization of XPF protein was observed in cells expressing a mutant in which XPF arginine 568 was replaced by lysine. Loss of CARM1 impaired XPF-ERCC1 accumulation at the site of damage and delayed removal of cyclobutane pyrimidine dimers by UV. As a result, CARM1-deficient cells showed increased UV sensitivity. Our results provide insight into the importance of CARM1 not only in the mechanism of XPF-ERCC1 complex stabilization but also in the maintenance of genome stability.
Authors
- Neil Q. McDonald (ORCID: https://orcid.org/0000-0003-0975-6325)
- Hiroyuki Niida (ORCID: https://orcid.org/0000-0001-7508-055X)
- Atsuo Ogura (ORCID: https://orcid.org/0000-0003-0447-1988)
- Masatoshi Kitagawa (ORCID: https://orcid.org/0000-0002-5819-048X)
- Chiharu Uchida (ORCID: https://orcid.org/0000-0002-9110-3755)
- Masaki Matsumoto (ORCID: https://orcid.org/0000-0002-6987-0288)
- Satoshi Sakai (ORCID: https://orcid.org/0000-0002-0056-1014)
- Akira Motegi (ORCID: https://orcid.org/0000-0002-8708-3958)
- Kenta Iijima (ORCID: https://orcid.org/0009-0004-1996-8940)
- Tatsuya Ohhata (ORCID: https://orcid.org/0000-0003-1124-6164)
- Atsushi Hatano (ORCID: https://orcid.org/0000-0002-0386-5080)
- Michiko Hirose
- Masahiko Ito
- Hirotada Akiyama
- Rin Ogihara
Institutions
- Kyoto University (JP)
- The Francis Crick Institute (GB)
- Hamamatsu University School of Medicine (JP)
- RIKEN BioResource Research Center (JP)
- Institute of Structural and Molecular Biology (GB)
- Niigata University (JP)
- Birkbeck, University of London (GB)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2025-04-22
- DOI
- https://doi.org/10.1093/nar/gkaf355
- Primary Topic
- Cancer-related gene regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministry of Higher Education and Scientific Research
- Wellcome Trust
- Francis Crick Institute
- Cancer Research UK
- Ministry of Education, Culture, Sports, Science and Technology
- Medical Research Council