Research Papers:

Loss of the N-terminal methyltransferase NRMT1 increases sensitivity to DNA damage and promotes mammary oncogenesis

Lindsay A. Bonsignore, Jill Sergesketter Butler, Carolyn M. Klinge and Christine E. Schaner Tooley _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:12248-12263. https://doi.org/10.18632/oncotarget.3653

Metrics: PDF 2084 views  |   HTML 3488 views  |   ?  


Lindsay A. Bonsignore1, Jill Sergesketter Butler1, Carolyn M. Klinge1, Christine E. Schaner Tooley1

1 Department of Biochemistry & Molecular Genetics, Center for Genetics and Molecular Medicine, University of Louisville School of Medicine, Louisville, KY, USA

Correspondence to:

Christine E. Schaner Tooley, email:

Keywords: DNA damage, DNA repair, breast cancer, N-terminal methylation, NRMT1

Received: November 13, 2014 Accepted: February 27, 2015 Published: March 26, 2015


Though discovered over four decades ago, the function of N-terminal methylation has mostly remained a mystery. Our discovery of the first mammalian N-terminal methyltransferase, NRMT1, has led to the discovery of many new functions for N-terminal methylation, including regulation of DNA/protein interactions, accurate mitotic division, and nucleotide excision repair (NER). Here we test whether NRMT1 is also important for DNA double-strand break (DSB) repair, and given its previously known roles in cell cycle regulation and the DNA damage response, assay if NRMT1 is acting as a tumor suppressor. We find that NRMT1 knockdown significantly enhances the sensitivity of breast cancer cell lines to both etoposide treatment and γ-irradiation, as well as, increases proliferation rate, invasive potential, anchorage-independent growth, xenograft tumor size, and tamoxifen sensitivity. Interestingly, this positions NRMT1 as a tumor suppressor protein involved in multiple DNA repair pathways, and indicates, similar to BRCA1 and BRCA2, its loss may result in tumors with enhanced sensitivity to diverse DNA damaging chemotherapeutics.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 3653