CARM1/PRMT4 facilitates XPF–ERCC1 heterodimer assembly and maintains nucleotide excision repair activity
Open Access
- 22 April 2025
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 53 (8)
Abstract
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.Keywords
Funding Information
- Ministry of Education (16K08580)
- Cancer Research UK (CC2068)
- Medical Research Council (CC2068)
- Wellcome Trust (CC2068)
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