Arginine methylation of human DNA topoisomerase I by PRMT5 facilitates DNA relaxation - PubMed
3 hours ago
- #Arginine Methylation
- #PRMT5
- #DNA Topoisomerase I
- PRMT5 symmetrically dimethylates human DNA topoisomerase I (Top1) at arginine residues R708 and R749.
- This methylation enhances Top1's DNA relaxation activity by improving strand rotation without affecting DNA binding.
- Methylation-deficient Top1 mutants show impaired mobility, accumulate more Top1-DNA covalent complexes under camptothecin (CPT), and delay Top1cc resolution.
- Loss of Top1 methylation, via mutation, PRMT5 knockout, or inhibitors, amplifies CPT-induced DNA damage.
- Combining PRMT5 inhibitors with Top1 poisons like irinotecan increases cytotoxicity in cancer cells and suppresses tumor growth and metastasis in a mouse model.