Armt1, also known as the product of the C6orf211 gene, has diverse functions. Structurally, it belongs to the DUF89 family. Biochemically, it functions as a phosphatase, targeting phosphate substrates like fructose-1-phosphate, potentially limiting the buildup of phospho-glycan species and related damaged metabolites [1]. It has also been characterized as a protein carboxyl methyltransferase that targets proliferating cell nuclear antigen (PCNA) in breast cancer cells, methylating glutamate side chains and being linked to the DNA damage response [2].

In breast cancer cell lines, shRNA-based knockdown of Armt1 expression led to different survival responses to genotoxic stress. SK-Br-3 cells showed increased sensitivity to UV, adriamycin, and MMS, while MCF7 cells exhibited increased resistance, laying the foundation for understanding its role in the DNA damage response mechanism [2].

In conclusion, Armt1 has multiple functions including phosphatase and methyltransferase activities. Its role in the DNA damage response, as revealed through loss-of-function experiments in breast cancer cell lines, is crucial. Understanding Armt1 can potentially provide insights into breast cancer development and treatment strategies related to the DNA damage response pathway.

References:

1. Dennis, Taylor N, Kenjić, Nikola, Kang, Amrik S, Clarke, Steven G, Perry, J Jefferson P. 2020. Human ARMT1 structure and substrate specificity indicates that it is a DUF89 family damage-control phosphatase. In Journal of structural biology, 212, 107576. doi:10.1016/j.jsb.2020.107576. https://pubmed.ncbi.nlm.nih.gov/32682077/

2. Perry, J Jefferson P, Ballard, Gregory D, Albert, Alexandra E, Malkas, Linda H, Hoelz, Derek J. 2015. Human C6orf211 encodes Armt1, a protein carboxyl methyltransferase that targets PCNA and is linked to the DNA damage response. In Cell reports, 10, 1288-96. doi:10.1016/j.celrep.2015.01.054. https://pubmed.ncbi.nlm.nih.gov/25732820/