Yang Li, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Travis D Kerr, Deepa Bisht, Yalong Wang, Sharad Awasthi, Babita Kaundal, Siqi Wu, Weiyi Peng, Marc L Mendillo, Yiling Lu, Collene R Jeter, Guang Peng, Jinsong Liu, Shannon N Westin, Anil K Sood, Michael T Lewis, Jishnu Das, S Stephen Yi, Mark T Bedford, Daniel J McGrail, Nidhi Sahni
Multiple cancers exhibit aberrant protein arginine methylation by both type I arginine methyltransferases, predominately protein arginine methyltransferase 1 (PRMT1) and to a lesser extent PRMT4, and by type II PRMTs, predominately PRMT5. Here, we perform targeted proteomics following inhibition of PRMT1, PRMT4, and PRMT5 across 12 cancer cell lines. We find that inhibition of type I and II PRMTs suppresses phosphorylated and total ATR in cancer cells. Loss of ATR from PRMT inhibition results in defective DNA replication stress response activation, including from PARP inhibitors...
December 19, 2023: Cell reports medicine