Perry, J. Jefferson P.Ballard, Gregory D.Albert, Alexandra E.Dobrolecki, Lacey E.Malkas, Linda H.Hoelz, Derek J.2015-07-152015-07-152015-03Perry, J. J. P., Ballard, G. D., Albert, A. E., Dobrolecki, L. E., Malkas, L. H., & Hoelz, D. J. (2015). Human C6orf211 Encodes Armt1, a Protein Carboxyl Methyltransferase that Targets PCNA and Is Linked to the DNA Damage Response. Cell reports, 10(8), 1288-1296.https://hdl.handle.net/1805/6560Recent evidence supports the presence of an L-glutamyl methyltransferase(s) in eukaryotic cells, but this enzyme class has been defined only in certain prokaryotic species. Here, we characterize the human C6orf211 gene product as “acidic residue methyltransferase-1” (Armt1), an enzyme that specifically targets proliferating cell nuclear antigen (PCNA) in breast cancer cells, predominately methylating glutamate side chains. Armt1 homologs share structural similarities with the SAM-dependent methyltransferases, and negative regulation of activity by automethylation indicates a means for cellular control. Notably, shRNA-based knockdown of Armt1 expression in two breast cancer cell lines altered survival in response to genotoxic stress. Increased sensitivity to UV, adriamycin, and MMS was observed in SK-Br-3 cells, while in contrast, increased resistance to these agents was observed in MCF7 cells. Together, these results lay the foundation for defining the mechanism by which this post-translational modification operates in the DNA damage response (DDR).en-USAttribution-NonCommercial-NoDerivs 3.0 United StatesArmt1DNA damageArticle