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

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

  • Cell Rep. 2015 Mar 3;10(8):1288-96. doi: 10.1016/j.celrep.2015.01.054.
J Jefferson P Perry 1,  Gregory D Ballard 2,  Alexandra E Albert 2,  Lacey E Dobrolecki 3,  Linda H Malkas 3,  Derek J Hoelz 4
Affiliations

Affiliations

  • 1 Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA; School of Biotechnology, Amrita University, Kollam, Kerala 690525, India.
  • 2 Maine Institute for Human Genetics and Health, Bangor, ME 04401, USA.
  • 3 Department of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
  • 4 Maine Institute for Human Genetics and Health, Bangor, ME 04401, USA; Department of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: hoelzd@husson.edu.
PMID: 25732820 DOI: 10.1016/j.celrep.2015.01.054
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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