Human C6orf211 encodes Armt1, a protein carboxyl methyltransferase that targets PCNA and is linked to the DNA damage response.
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).
Department of Biochemistry, University of California, Riverside, Riverside, CA 92521, USA; School of Biotechnology, Amrita University, Kollam, Kerala 690525, India.
J Jefferson P
JJ
Perry
Maine Institute for Human Genetics and Health, Bangor, ME 04401, USA.
Gregory D
GD
Ballard
Maine Institute for Human Genetics and Health, Bangor, ME 04401, USA.
Alexandra E
AE
Albert
Department of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Lacey E
LE
Dobrolecki
Department of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Linda H
LH
Malkas
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.
Derek J
DJ
Hoelz
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D061986:MCF-7 Cells; D008745:Methylation; D008969:Molecular Sequence Data; D018809:Proliferating Cell Nuclear Antigen / Q000737:chemistry / Q000378:metabolism*; D011497:Protein O-Methyltransferase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D016415:Sequence Alignment; D013379:Substrate Specificity
D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; C000602988:Armt1 protein, human; D011497:Protein O-Methyltransferase