Human C6orf211 encodes Armt1, a protein carboxyl methyltransferase that targets PCNA and is linked to the DNA damage response

Cell Reports
J Jefferson P PerryDerek J Hoelz

Abstract

Recent 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).

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Citations

Jun 21, 2016·Nature Chemical Biology·Lili HuangAndrew D Hanson
Jan 11, 2017·The Journal of Cell Biology·Bradlee NelmsWayne Lencer
Jun 28, 2020·Hormones & Cancer·David K LungElaine T Alarid
Jan 16, 2019·Breast Cancer Research : BCR·Joshua HoffmanElad Ziv
Oct 10, 2015·Oncotarget·Derek Hoelz
Jul 19, 2020·Journal of Structural Biology·Taylor N DennisJ Jefferson P Perry

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